CLS - From Research to Commercialization Part 3. – The page is about to be turned

2019-04-02 06:19, Edited at: 2019-04-03 12:56

The Swedish innovator in immunotherapy against cancer is now only a few days away from the largest clinical presentation made thus far by the company. The co-founder together with two research leaders and an expert in immunology will inform the audience at ECIO about imILT's clinical journey, current results and discuss what the future holds for imILT .

The recap

In the early years, Professor Karl-Göran Tranberg made the discovery that, under controlled conditions, heat from laser beams could destroy cancerous cells locally, and simulataneously, stimulate the immune system to attack cancer in the entire organism, the latter discovery gave birth to the imILT method. Following a series of successful treatments, CLS was founded (2006) by Karl-Göran Tranberg, Pär Henriksson and Lars-Erik Eriksson with the intent to ​​commercialize the Tranberg Thermal Therapy system together with the flagship method, imILT. CLS went on to win the Swedish Venture Cup South and was thereafter listed on Aktietorget, a Swedish OTC market (Today called Spotlight Stock Market). During the years that followed, the system and products were developed and optimized, they were CE certified and the application for market approval was submitted to the FDA in the US. Furthermore, CLS simultaneously developed the system to enable percutaneous treatment (treatment through the skin).

In 2015, CLS received its marketing approval from the FDA and also received an invitation to participate in a study together with one of Europe's foremost clinics specializing in the treatment of pancreatic cancer. The University clinic in Verona, Italy, initiated and funded the study itself while they collaborated their study efforts together with Institute Paoli-Calmettes in Marseille, France.

In 2016, CLS received one of the largest project grants from the EU program Horizon 2020. The project included the implementation of three clinical trials. This year, CLS also compiled and published its first Post-Market Clinical Follow-up report, which was based on eight imILT treatments using the Tranberg system. In this report, CLS was able to state that no serious side effects had occurred that could be linked to the treatments performed. The system was therefor considered as safe provided that the treatment instructions were followed. Later that year, CLS also signed a letter of intent with The Department of Radiology at the University of Texas Medical Branch (UTMB). As a token of his great work, the CEO, Lars-Erik Eriksson, was awarded the title "Best CEO in MedTech" by the leading magazine European CEO.

In 2017, CLS entered into an intensive period and received its first order for the Tranberg system from a leading cancer hospital in the US. Furthermore, the Focal Laser Ablation (FLA) method against prostate cancer became one of the company's business legs. CLS then enters an acquisition of the German company LMTB with all its patents for the important fiber technology that forms the basis of the world-unique non-cooled diffuser fiber that CLS today markets. 

Shortly thereafter, CLS received an approval from the FDA to market this unique product and at the same time CLS received an important basic patent approval in Europe. The same year CLS participated for the first time as one out of 15 European champion companies at BIO in San Diego, USA. 

The company's products also came to be evaluated for laser ablation using MRI-guidance, which was seen as a prerequisite for advancement in the FLA market. 

During the latter part of the year, CLS products also became subject of use in a new field, veterinary oncology, through a study initiated by, Din Veterinär. This first of its kind trial in Sweden is fully funded by Sveland Animal Insurance.

In the mist of this intensive year, CLS simultaneously announced that its products were being evaluated for treatment of vascular malformations by a leading hospital in the United States. Furthermore, in 2017, CLS received a strong patent in China and through its R&D was also able to expand its product portfolio with another variant of the unique non-cooled diffuser fiber. At the end of the year, the company received further orders from clinics in the US serving as proof of concept.

In early 2018, CLS announced that imILT treatments for pancreatic cancer showed a positive trend in terms of survival rate. 

During the spring, CLS also initiated its first study dedicated to the FLA method, this trial was announced together with Toronto General Hospital in Canada. CLS then proudly told the market that the FDA had approved the company with praise for its quality processes. 

By mid-2018, CLS announced that it had entered into a memorandum of understanding with Canadian firm, Exact Imaging, a company which is a world leader in micro ultrasound. A technique whose image resolution far exceeds traditional ultrasound and can compare itself with MRI in resolution and image quality at very competitive price. 

CLS also signs an agreement with the French company Image Guided Therapy to develop and commercialize a software product for MR-controlled temperature monitoring.  

A few months later, the pioneers in FLA treatment for prostate cancer, Desert Medical Imaging in the US, selects CLS products to be included in their long-term clinical study.

In October 2018, CLS signed two agreements with a US based company called MRI Interventions Inc. The first deal related to licensing of CLS technology and development of next-generation platforms, in navigation and laser ablation for use, in surgical procedures in the spine and brain. The agreement grants an exclusive global license to MRI Interventions, for current and future products, and for intellectual property rights, in neuro and spinal surgery. CLS will be the exclusive manufacturer of all products under the agreement, and own the rights for all areas of application outside of neuro and spinal surgery. 

The second agreement stated that MRI Intervention's was granted a two year period of exclusive right to distribute and sell CLS products, in the US and Canada, for use in any other interventional MRI-guided treatment than in the spine and brain.

In November 2018, CLS announced that for five of the patients who received imILT treatment for advanced pancreatic cancer, 17 months of overall survival was noted, which is significantly longer than previously published results for conventional treatments.

So far in 2019, CLS has signed an agreement with one of the giants in the market. Siemens Healthineers and CLS entered into an agreement concerning optimal adaptation of the Tranberg system to Siemens' world-leading portfolio of MR scanners through the Access-I software. 

This year, we have also seen Dr. Eric Walser, a CLS consultant and customer, publish his results for 120 patients treated with Focal Laser Ablation against low to intermediate risk prostate cancer. The results are very encouraging and indicate that FLA is a treatment with an extremely low amount of side effects and functional impact, but at the same time, yet a very effective method of curing prostate cancer with exceptionally few relapses.

Just days away, on April 8 to 11th, CLS will hold a hands-on workshop (ie educational training) at ECIO and for the first time host a more than an hour long symposium were the co-founder and research experts will reveal the trial results.

For those who are unfamiliar with European Conference of Interventional Oncology (ECIO) this is a recurring event and is one of the largest and most important events for interventional radiologists and in general for oncology in Europe.

Below is an excerpt from ECIO's program in regards to what CLS will be presenting.

Modification of laser ablation produces strong immune stimulatory effects

Moderator: A.H. Mahnken (Marburg / DE)

• Introduction
• A.P. Mahnken (Marburg / DE)
• Abscopal effect - a case report
• B. Gonçalves (Porto / PT)
• Immune stimulating interstitial laser thermotherapy (imILT) - the scientific background
• K.-G. Tranberg (Lund / SE)
• imILT - in immunological context
• G. Hedlund (Lund / SE)
• Laser ablation on Locally Advanced Pancreatic Cancer (LAPC) - clinical results, surgeon's view
• O. Turrini (Marseille / FR)
• imILT - future aspects
• B. Gonçalves (Porto / PT)

Author note: During the past years, shareholders hav expressed some frustration with the company due to its limited communication in regards to treatment outcomes. Now, CLS seems to have turned the page and the choice of the title “Modification of laser ablation produces strong immune stimulatory effects“, seems to be a clear indicator that the brakes are finally of and that the company now has additional evidence backing its clinical claims. 

From a business point of view, one can argue that the current repetitive orders are validation enough and a sign of "proof of concept". However, in the context of clinical evidence, it's measured in terms of treatment outcomes and ultimately the rate of survival.

CLS sees a clear positive trend in terms of survival for patients receiving imILT treatment, but now, with ECIO closing in, we may soon get a deeper insight to these fundamentally important results.

The speakers

Dr. Belarmino Gonçalves

Interventional radiologist and expert researching endovascular procedures and specializing in minimally invasive methods within oncology. He’s the principal investigator for CLS’s H2020 sponsored clinical study in Porto, the study is still ongoing in regards to follow-up, but the arrangement was such that two randomized cohorts were included, one in which patients were treated with imILT and one in which patients received standard cytostatic drugs. 

Dr. Gonçalves is also the doctor who, outside clinical studies, treated a middle-aged man 4 years ago with imILT. The patient suffered from advanced pancreatic cancer (stage IV) with metastasis in the liver. CLS has continuously reported this patient as being a success story itself, during the course of these years the improvements were of such nature that the man was able to return to his work. 

At the moment he as survived his disease for 4 years and such long survival for patients with this diagnosis is very rare indeed. What is known is that the patient has received a total of three treatments and given the headline seen above regarding a case study concerning abscopal effects one could expect Dr. Gonçalves to reveal new details regarding this middle-aged man’s battle along with his remarkable survival through the aid of the imILT treatment.

Prof. Karl-Göran Tranberg

Professor of Surgery, discoverer and researcher of imILT, co-founder of CLS and Senior Medical Advisor. He is the reason and passion personified that took this discovery on a path to clinical adoption. Prof. Tranberg, found a way to crack the cancer cells wall of defense and more precisely this means, the way in which heat is applied to a solid tumor in just the right way. 

“About 46 degrees in half an hour is perfect, according to Karl-Göran Tranberg. At lower temperatures, the tumor does not die. At higher temperatures, the antigens coagulate and the immune system is not activated.”

Prof. Tranberg’s early work and his continued research during a time of 15 years in the field of interstitial laser therapy laid out many of the pavestones needed to build a clinical and commercial success story around the company CLS. During this time 72 patients were treated and some of which were deemed incurable and wouldn’t survived if only treated with conventional surgery at the time. The results spoke for themselves, showing both prolonged survival and most importantly some patients were cured.

Dr. Olivier Turrini

Head of the Marseille trial were imILT treatment were given to five patients suffering from unresectable locally advanced pancreatic cancer. Dr. Turrini who is an experienced surgeon, will at ECIO give his perspective to the imILT treatment in a surgical context. This perspective is indeed a very important and interesting one since the patients he treated could not be treated with surgery but instead were treated with imILT. The outcome of these treatments could mean that patients who had to rely on chemo, a treatment regimen that generally decreases the quality of life and statistically doesn’t mean a cure, now has a new treatment choice which actually helps and could mean a cure.

Prof. Gunnar Hedlund

Senior Scientific Advisor PhD Assoc Prof Tumor Immunology. Prof. Hedlund is attending ECIO as an expert in immunology and will give his scientific view of the imILT treatment in a immunological context. The way the laser induced heat cracks open the cancer cells defense walls and how the controlled temperature allows for antigen to leak out and present itself to the signaling immune cells that activate an immunological reaction were T-cells kill remaining cancer cells as well as vaccinate the body from recurrence is about to be declared by Prof. Hedlund. 

The gravity of these biological reactions has been shown so useful and important that it has spun a paradigm shift in cancer treatment. Much of the basic principles that surround checkpoint based immunotherapy that was recently awarded the Nobel Prize has direct links to how the imILT treatment works. Immunotherapy consists of several different approaches and different tools to engage the reaction but they all harness the same weapon, the patient’s own immune system, against the cancerous disease. Prof. Hedlund’s perspective will shine new light on these mechanisms that shape and cure our bodies.

The takeoff

The journey from laboratory research to prototyping and product development to clinical practice could be argued to never end for a life science company since the continued R&D ensures both commercial progress but most importantly enhances clinical outcome.

With that said, CLS has now reached the moment were the company has built a platform from which it will launch its market disrupting cancer treatment, imILT. 

Now, backed with clinical results and commercial partners such as Exact Imaging, IGT, MRI Interventions and Siemens Healthineers, CLS will move forward and imILT treatments will be made available to paying customers in Porto, Portugal at the hands of Dr. Belarmino Gonçalves. Most likely Dr. Turrini soon will follow his lead and given the positive outcome of the ECIO presentations the next clinical phase would be to initiate a larger multi-institutional clinical trial. A trial which preferably will be co-managed with a partner in the immunotherapy market but given the already existing dialog between CLS and Siemens Healthineers, the financial and clinical partnership for this final step could be well on the way already. 

CLS is not only launching imILT this year, it’s also creating a new source of income through the partnership with IGT were its developing a software product for guidance and monitoring of the procedures. This product will serve as the platform from which MRI Interventions will more broadly launch CLS products for use in the FLA market in United States and Canada. During the second half of this year MRI Interventions will start to commercialize CLS products for the use in neuro- and spine surgery through a global licensing deal between CLS and MRI Interventions. Further, CLS will through the partnerships with Siemens, IGT and MRI Interventions address the share of the market that carry out these laser-based treatments with the help of a magnetom scanner (MRI). 

In a parallel business track, CLS will through its partnership with Exact Imaging, launch a joint product offering that will allow the two companies to offer a very competitive system that offers both biopsy and treatment for prostate cancer and BPH. The products will interconnect within one workflow under the guidance of Exact Imaging’s leading micro-ultrasound system and treatment rationale of the Tranberg system to allow the practitioners an unique workflow setup at a competitive price. 

CLS has through these partnerships solved both distribution and gained access to an formidable sales force while enhancing its product offering through attractive partnership deals. The company has in such terms done very well for itself by creating proper platforms to launch its products on a global scale. Now with eyes turning to ECIO, which is just days away, the attendees will be made aware of imILT’s disruptive power and its share importance to cure difficult tumor diseases.

Needless to say but the upward potential of this stock is something extraordinary, the current valuation of approximately 440 MSEK is 1/7 of the value that the co-founder Pär H Henriksson estimated as a “lowest price” for the company at that given moment back in January this year when I interviewed him. 

“I mean that everything under ten times the current valuation feels low if you compare with similar companies with a finished CE-marked product and a number of completed treatments with excellent results.” /Pär H Henriksson, Co- Founder CLS.

Few would certainly argue that the value for a company with an effective immunotherapy against solid cancers and products that enable such a great diversity of use for the practitioners would be worth less than three billion SEK. Instead, the many would probably argue that it’s a price far below what such an exceptional method and device would truly be worth. But most importantly, for the patients, the imILT method is on the right way to prove itself to be invaluable.