Home Interviews Stayble Therapeutics – treating the underlying cause of back pain

Stayble Therapeutics – treating the underlying cause of back pain

Stayble Therapeutics – treating the underlying cause of back pain

3 July, 2021
The idea of transforming a spinal disc into connective tissue in order to cure discogenic chronic low back pain came to Kjell Olmarker while waiting for a delayed flight. The idea became the basis for Stayble Therapeutics and the injectable drug STA363. The company is now conducting a phase IIb study that follows upon successful phase Ib results. BioStock has spoken with the company’s CEO Andreas Gerward about the treatment, the ongoing study, and the company’s future prospects.

Stayble Therapeutics’ treatment targets the underlying cause of discogenic chronic low back pain (clBP), i.e. back pain caused by disc degeneration. Today, a large part of this patient group, whose everyday life is thus fraught with both chronic pain and limited mobility, lack adequate treatment. This in turn leads to reduced quality of life and ability to work, which results in large societal costs. Stayble Therapeutics – which has been listed on the Nasdaq First North Growth Market since March 9th 2020 – wants to remedy this through its drug candidate STA363.

A delayed flight led to the idea

The company was founded in 2015 by Professor Kjell Olmarker at the Institute of Biomedicine, Sahlgrenska Academy. The idea of transforming a spinal disc to connective tissue came to him when he was waiting for a flight home after attending a conference on low back pain and back surgery.

He was pondering how to deal with the very cause of back pain. Olmarker knew that the discs in the back begin to degenerate in the early twenties, which leads to cracks and instability in the disc as well as leakage of inflammatory substances. This process irritates the nerves within and outside of the disc which causes pain. Once you reach the age of 65-70, the disc stabilises, and this type of back pain often disappears. This fact made Olmarker think that it should be possible to replicate the natural process by actively transforming the disc to connective tissue.

The technology has the potential to cure low back pain

Olmarker’s idea forms the basis for Staybles Therapeutics’ injectable drug STA363, which basically consists of lactic acid together with a contrast agent. STA363 is based on an endogenous and well documented substance that transforms the spinal disc to connective tissue. Therefore, it has the potential to accelerate the healing process for disc degeneration so that it only takes a few weeks, or months, instead of having to wait 30-40 years for the body’s self-healing process.

Stayble’s treatment is aimed at patients who suffer from discogenic chronic low back pain and do not improve through analgesics and physiotherapy. The treatment focuses on the two underlying causes of back pain – leakage of inflammatory substances and instability in the segment.

During the treatment, an injection needle is placed in the affected disc with the help of X-ray. STA363 is then injected directly into the disc which triggers the cells to produce connective tissue. This re-stabilises the intervertebral segment and restricts leakage of pro-inflammatory agents. The patient can thus become pain-free in the long term, without having to repeat the treatment or undergo extensive rehabilitation.

Previous study results give good hopes for ongoing study

The company has successfully conducted a phase Ib study with 15 patients where 3 different doses of STA363 and placebo were tested. The study showed positive results regarding the safety, tolerability and desired biological effect of the treatment in the disc. A transformation to connective tissue in the disc was found in patients treated with a medium or high dose of STA363, but not in those who received placebo or the lowest dose of STA363.

The phase Ib results motivated the company to advance the project to the next stage of development – to conduct a phase IIb clinical study. This study is currently underway and aims to confirm the candidate’s safety and tolerability as well as to demonstrate clinically relevant reduction in pain after treatment with STA363 in patients with discogenic chronic low back pain.

Included patients will be treated with either a high or medium dose of STA363 or placebo. They are then monitored for a 12-month period. The study will cover circa 100 patients in total and will be carried out at 20 clinics in the Netherlands, Russia, and Spain. During the summer, it was announced that patient recruitment had begun.

Back pain causes everyday problems for millions of people

100 million people are estimated to live with disc-related chronic low back pain in the largest, and perhaps most important, markets – the USA, Japan and the EU5. Stayble Therapeutics estimates that about 30 million individuals are expected to benefit from treatment with STA363. Every year, 11.5 million new individuals are diagnosed with disc-related chronic low back pain in these markets, of which 3.5 million are suited for treatment with STA363.

A typical patient is usually between 20-50 years old, and in some cases up to 60 years. For them, the back pain creates significant everyday problems; they may have difficulty lifting their children, going for walks, flying, going to the cinema or even putting on their socks in the morning.

Major socio-economic consequences and opioid misuse problems

Back pain is one of the main reasons for sick leave, which results in both high production losses and costs to the welfare society. It is also in the top when it comes to socio-economic costs – both indirect and direct ones.

In recent years, there has been much discussion regarding overconsumption and misuse of analgesic opioid drugs in the treatment of chronic back pain. Opioid drugs are strong painkillers, but at the same time very addictive often leading to addiction. As with most addictions, fatal overdoses are not uncommon.

The United States in particular has a major problem with overprescription of opioids – 50 per cent of the patients who use opioids in the United States state chronic back pain as the reason for receiving the medication. This has resulted in widespread opioid misuse with high death rates as a consequence. In light of this, the need for new, effective treatments for chronic back pain becomes even more obvious. Stayble Therapeutics’ STA363 has the potential to reduce patients’ pain and disability – and thereby improve the quality of life for millions of people – without the risk of misuse and mortality.

BioStock has previously written several articles on the problem of opioid treatments. See for example Jakten på alternativ till opioider – vår tids heliga Graal?

The CEO comments on the company, product and future prospects

BioStock has contacted Andreas Gerward, CEO of Stayble Therapeutics since 2015, to find out about his views on the potential for the company’s treatment.

Andreas Gerward, CEO Stayble Therapeutic

Andreas Gerward, can you start by telling us what attracted you to the role of CEO at Stayble Therapeutics?

– It was the simplicity of the concept and the opportunity to fill a great medical need for a number of patients that appealed to me! For me, one of Stayble’s most significant benefits is that we focus on treating the underlying causes of the pain instead of just relieving the symptom.

– I have been involved in the company’s entire journey from idea, through preclinical and early clinical studies, to where we are today with a multinational phase IIb study underway. The journey has been incredibly exciting, and I look forward to leading Stayble through the next step.

You mention that it was the simplicity in the concept that appealed you, can you develop this thought further?

– Transforming an unstable and leaking disc into connective tissue and thus stabilising the back segment and preventing leakage feels like an intuitively correct way to treat the underlying causes of back pain. The fact that we use the body’s own substance that naturally causes connective tissue transformation and symptom relief reduces the risk during the development process for our candidate STA363, both in terms of safety and effect.

Can you, in short, explain how lactic acid can induce connective tissue transformation and how connective tissue transformation in the spinal disc can reduce back pain?

– STA363 converts the gelatinous disc nucleus into connective tissue (collagen), which leads to increased stability. This is believed to reduce the production and leakage of painful inflammatory molecules.

–The mechanism of action at the molecular level is thought to be due to stimulation of collagen I synthesis – a mechanically robust form of collagen – in cells found in the disc nucleus. In addition, STA363 is believed to increase the formation of a special type of cell that continuously has a very high production of collagen.

How are people with chronic discogenic low back pain treated today, and what shortcomings do you see with these treatment options?

– Today, people with chronic discogenic low back pain are treated primarily with physiotherapy and analgesics. However, only about 30 per cent of patients improve with this treatment. The last resort is to undergo surgery (spinal fusion) which approximately 1 per cent of patients choose to do. The operation is both expensive and associated with certain risks and also requires long-term sick leave and rehabilitation.

– The great medical need in chronic discogenic low back pain and the lack of effective treatment options is the background to why Stayble Therapeutics was founded.

»Our vision is to be able to offer the patient a simple and effective treatment that attacks the underlying cause of the back pain and provides lasting relief of the symptoms.« – Andreas Gerward, CEO Stayble Therapeutics

What are the main advantages of your treatment compared to existing alternatives?

– Physiotherapy and analgesics ”only” remove the pain – i.e. take away the symptoms – without removing the underlying cause. In addition, it does not help all patients.

– Our treatment is cost-effective, unlike spinal surgery which also requires extensive rehabilitation. In other words, there are no effective treatment options today for patients with chronic disc-related back pain.

–We hope to be able to change this situation with STA363. Our vision is to be able to offer the patient a simple and effective treatment that attacks the underlying cause of the back pain and provides lasting relief of the symptoms.

How will you position STA363 – do you intend to target a specific group of patients with chronic low back pain?

– STA363 will target patients suffering from chronic low back pain due to disc degeneration. We see the treatment as an alternative when conservative treatment with physiotherapy and analgesics does not work. A typical patient is usually between 20-50 years old, in some cases up to 60 years old. But we can see potential in other patient groups as well in the long run, e.g. patients with neck problems.

Tell us about the design of the phase IIb clinical study and what you think and hope that the study results will mean for Stayble Therapeutics!

– The primary goal of the study is to demonstrate a statistically significant and clinically relevant reduction in pain. The pain is measured with a numerical rating scale between 0 to 10, which means no pain at all (0) to extreme pain (10), 6 months after treatment. Patients will be monitored for 12 months to better understand the long-term effects of STA363. Stayble will use improved methods to reduce the placebo effect and variability compared to other studies with the hope that the precision of the measurements will be higher than normal.

– A positive outcome for the study would mean that we have succeeded in achieving our most important milestone to date – to demonstrate a statistically relevant pain reduction with STA363. Based on such a result, we see good opportunities to initiate exciting collaborations to take the project further through clinical development, all the way to a market approval and launch.

So far, clinics have been initiated in the Netherlands and Russia. When do you expect to be able to initiate clinics in Spain as well?

– That’s right and we are very pleased to have succeeded in starting the study in the Netherlands and Russia and thereby keeping to the communicated schedule – despite the current Covid-19 situation. The goal is to initiate the clinics in Spain in October.

»In our phase Ib study, we have confirmed that STA363 is safe and tolerable and we have not identified any treatment-specific side effects or negative lasting effects.«

Based on the data you have so far – what does the side effect profile of STA363 look like?

– In our phase Ib study, we have confirmed that STA363 is safe and tolerable and we have not identified any treatment-specific side effects or negative lasting effects. Injecting into a diseased disk hurts, but it is a short-term pain that passes. The pain arises both when we inject placebo and STA363.

– The fact that STA363 consists of lactic acid, which is a well-known and body-specific substance, means that the risk that we will discover serious side effects in future studies is low.

Suppose you succeed in proving that STA363 reduces low back pain in your intended patient group – when do you think the candidate will be able to reach the market and what market impact do you expect?

– If everything goes as we envisage in the phase IIb study, we intend to enter into a collaboration with a major player to carry out a phase III study. The plan is for the study to be carried out as two parallel studies in Europe and the USA in order to subsequently be able to apply for market approval. With positive results also in phase III, a launch could potentially take place within 8-10 years.

– Today, the biggest challenge for those who suffer from chronic disrelated back pain is that there is a lack of treatments for the cause of their pain, which means that it remains chronic. If Stayble could launch a product that changes that, and really manages to alleviate the pain in the long term, it would have a huge market impact.

– The doctors we have talked to testify to the lack of alternatives and a great willingness to be able to offer something that can help this patient group. At the same time, the patients say that they would do almost anything to reduce their pain. These testimonials indicate a very attractive market potential for Stayble Therapeutics and STA363.

Could you describe your business model more in detail?

– Stayble’s business model is to drive the development of STA363 on our own through the phase IIb study and then seek partners for further development and commercialisation. Our revenue model is therefore based on milestone payments and royalty income on future sales.

»The transformation that STA363 induces is permanent, which is not the treatment effect of stem cell therapies«

Are there any competitors in the market that develop treatments similar to STA363? If so, how does it affect your view of the competitive situation at a future market entry?

– Available treatments for disc-related back pain mainly consist of physiotherapy, painkillers and back surgery. These treatments are positioned differently than STA363 would be.

– The competition is thus in the form of other research companies, primarily those that focus on stem cell therapies. Injection of stem cells aims to rejuvenate the disc and reverse the development of the disease. The technology has not yet proven successful and involves major challenges, including getting stem cells to survive in the very inhospitable oxygen-poor environment in a degenerating back disk. The long-acting effect of stem cell treatment is also uncertain as the disc continues its degenerative process. The most advanced stem cell therapy project for back pain is in a phase III clinical trial and is owned by the Australian company Mesoblast Ltd.

– If any stem cell project were to succeed, it would be a competitor to STA363. However, STA363 has great advantages in the form of a much simpler mechanism of action and substance, but above all in terms of the long-term effects of the treatment. The transformation that STA363 induces is permanent, which is not the treatment effect of stem cell therapies.

Speaking of the competitive landscape- what does your IP protection look like?

– We have two patent families that protect the use of lactic acid for the treatment of back pain. The patents have priority dates from 2014 and 2015, respectively, and are thus valid until 2034 and 2035. We have received approvals in Europe, the USA, China, Japan and Russia, among others. The IP protection provides the protection we need for further development of Stayble Therapeutics’ treatment concept.

You have an IP protection that indicates areas of use outside the lumbar spine. Do you intend to broaden your indication in the future?

– Our main area is the lumbar spine and this is also where the largest market is. Once we have proven that STA363 works in the lumbar spine, there are similar problems in the neck that could potentially be included in a broadening of indication – but that will be a question for the future.

If we continue to look ahead, where do you expect Stayble Therapeutics to be in three years?

– We are developing a very exciting drug in an area that affects a lot of people. Chronic disc-related low back pain has a significant negative impact on the quality of life and today’s treatments unfortunately do not provide much comfort. It is also characterised by inefficiency, the risk of side effects, high costs, and long rehabilitation times. With STA363, we want to offer this severely affected patient group a better everyday life by providing a simple and effective treatment that targets the underlying cause of back pain and provides lasting symptom relief.

– Our plan is to deliver, hopefully, positive phase IIb results during the first half of 2022 that underline STA363’s treatment effect. In three years, we hope to have advanced the discussions with potential partners. Then we are ready for a market-preparatory phase III study with STA363 which, if all goes well, we will carry out together with a long-term partner with strong resources.

The content of BioStock’s news and analyses is independent but the work of BioStock is to a certain degree financed by life science companies. The above article concerns a company from which BioStock has received financing.

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