Fighting the pandemic of antimicrobial resistance

This is the first article in the new series Start-up Spotlight, which features the most promising start-ups from the Norwegian health clusters.

AdjuTec Pharma is preparing the company’s First-in-Human phase I clinical trial.

The Norwegian start-up company AdjuTec Pharma has developed a new antibiotic product in the fight against antimicrobial resistance (AMR), which is now ready to be tested in humans. The final product will be administered intravenously to severely ill patients infected with bacteria resistant to existing treatments.

AMR is a global challenge, where increasing number of pathogenic bacteria become resistant to existing antibiotics. Despite the relatively low number of AMR cases in Norway compared to other countries, there is a rise in AMR-affected individuals, according to a 2023 report from the Norwegian Institute of Public Health.

“Antimicrobial resistance is threatening modern healthcare. Physicians are running out of last-resort antibiotics for treatment of high-risk infections and as prophylaxis in for example cancer therapy and major surgical procedures” commented Bjørn Klem, CEO of AdjuTec Pharma.

Eliminating the bacteria’s defense

AdjuTec Pharma has developed APC148, an enzyme inhibitor that works on gram negative bacteria. Gram negative bacteria are resistant to multiple antibiotics and listed by the World Health Organisation as the leading cause of deadly bacterial infections in the world.

“Bacteria defend themselves by producing enzymes that destroy antibiotics. APC148 inhibits these enzymes and thereby protects the antibiotic. This restores the activity of the antibiotic – saving patients’ lives,” explained Bjørn Klem.

Based on cutting-edge Norwegian research

The unique technology was developed by Professor Pål Rongved’s research group at the University of Oslo. Rongved is the founder of AdjuTec Pharma and was supported by Oslo Cancer Cluster Incubator to negotiate a licensing agreement with the University of Oslo and for obtaining the initial private funding.

The product has already been tested and validated in animal models. Now the phase IA trial will determine how APC148 behaves in the human body (pharmacokinetics) and evaluate the safety of the compound. The trial will involve groups of healthy volunteers who will receive single escalating doses. The first results are expected already early 2025. The phase IB trial starting in 2025 will then investigate how the APC148 works in combination with a broad-spectrum antibiotic.

Adjutec Pharma is a part of Oslo Cancer Cluster Incubator and currently located at Rebel in Oslo. Photo: Fartein Rudjord

A one-of-a-kind invention

Bacteria produce two kinds of enzymes, serine-ß-lactamases (SBLs) and metallo-ß-lactamases (MBLs). There are SBL-inhibitor products on the market, however no MBL-inhibitor products.

“APC148 has a unique mechanism-of-action versus other MBL-inhibitor products in pipeline making this a first-in-class product candidate,” said Bjørn Klem.

AdjuTec Pharma has ambitious plans for the enzyme inhibitor, aiming to combine it with various antibiotics.

“APC148 can be combined with different broad-spectrum antibiotics, including carbapenems and cephalosporins. After intravenous administration, APC148 should preferably have comparable pharmacokinetics, meaning plasma profile, distribution and route of elimination from the human body as the antibiotic. There should be no interactions between the compounds,” explained Bjørn Klem.

Commercial opportunity

AMR is growing at an alarming rate and MBL-producing bacteria will be a big challenge to the health care system for years. There is therefore a high unmet medical need targeting the class of bacteria enzymes called MBLs.

“Hardly any modern antibiotics on the market work against MBL-producing bacteria and we now have a technology at hand that can become a game-changer,” commented Bjørn Klem.

 

The series The Start-up Spotlight and The Scale-up Spotlight are produced in collaboration between the Norwegian health clusters: Norway Health Tech, Oslo Cancer Cluster, The Norwegian Smart Care Cluster, The Life Science Cluster and Biotech North. The initiative was funded by Viken fylkeskommune. Please contact us, if you wish to have your company to be featured.

Cell therapy breakthroughs in cancer treatment

The Section for Cellular Therapy’s Translational Research Unit in Norway has recently published two groundbreaking studies demonstrating the potential of cell-based therapies in the fight against cancer. The research group used the Oslo Cancer Cluster Incubator labs to develop pre-clinical treatments.

The collaborative team from Oslo University Hospital and the University of Bergen have made significant progress towards developing more effective and targeted treatments for advanced and treatment-resistant cancers.

Tackling colorectal cancer resistance

The first study, titled “Transient TCR-based T-cell therapy in a patient with advanced treatment-resistant MSI-high colorectal cancer,” focuses on a novel approach utilizing T-cell therapy to treat metastatic colorectal cancer. Published in a reputable journal, the study details the successful and safe application of a transient T-cell receptor (TCR) therapy named Radium-1 in a patient with advanced colorectal cancer resistant to conventional treatments. The therapy is named Radium-1, as it was discovered at the Radium Hospital (now part of Oslo University Hospital).

Dr Else Marit Inderberg, one of the lead researchers, explains the rationale behind their approach, stating,

“We aimed to modify the immune system to recognize and destroy tumour cells effectively. We transferred TCRs from responsive patients to non-responding ones, leading to promising results in our clinical trial.”

The therapy involves modifying a patient’s T cells to express the Radium-1 TCR using messenger RNA (mRNA) technology. Despite the challenging nature of advanced colorectal cancer, the treatment was well tolerated by the patient and resulted in stable disease, offering hope for further investigation in larger clinical trials.

Breakthroughs in ovarian cancer treatment

The second study, titled “Efficient CAR T cell targeting of the CA125 extracellular repeat domain of MUC16,” introduces a novel Chimeric Antigen Receptor (CAR) T-cell therapy targeting ovarian cancer. Ovarian cancer remains a significant challenge due to late-stage diagnosis and chemoresistance, making the development of new therapeutic strategies imperative.

Co-author Christopher Forcados and lead author Nicholas P. Casey. Photo: Oslo Cancer Cluster

Dr Nicholas P. Casey, the lead author of the study, emphasizes the importance of their research, stating, “Our CAR T-cell therapy targeting the CA125 extracellular repeat domain of MUC16 shows promising efficacy in preclinical models, offering a potential breakthrough in ovarian cancer treatment.”

The CAR T-cell therapy has shown promising results in both in vitro experiments and patient-derived xenograft mouse models. This paves the way for future clinical trials aimed at advancing CAR T-cell therapy for ovarian cancer patients. The development of these therapies took place in the fully-equipped laboratories of Oslo Cancer Cluster Incubator, specifically designed for carrying out these processes.

New hope and results ahead

These pioneering studies highlight the transformative potential of cell-based therapies in revolutionising cancer treatment. With further research and clinical validation, these innovative approaches could offer new hope for patients battling advanced and treatment-resistant cancers, and getting closer to realizing the vision of personalized and targeted cancer therapy.

As Dr Sebastien Wälchli, co-author of the studies, fittingly summarizes, “These findings underscore the importance of collaborative research efforts in advancing cancer immunotherapy and signify a significant step forward in our ongoing battle against cancer.”

The research group is anticipating the publication of a third article, which is expected to contain groundbreaking results. Stay tuned for further updates.

What is T-cell therapy for colorectal cancer:

Imagine your body has soldiers called T cells. These cells can recognize and fight against harmful things like cancer cells. In this therapy, scientists take T-cells from a patient’s body. Then modify these T-cells in a lab to make them better at recognizing and attacking cancer cells. It’s done by giving the T-cells a special weapon called Radium-1.

However, these modified T cells don’t stay in the patient’s body permanently. Instead, they are given back to the patient temporarily. These modified T cells go on a mission to find and destroy cancer cells. Even though they’re only there briefly, they can still make a big impact in fighting cancer cells.

What is CAR T-Cell Therapy for Ovarian Cancer:

In this therapy, scientists create special T cells called CAR-T cells. These T-cells are trained to recognize a specific target on ovarian cancer cells called MUC16. These CAR-T cells are specifically designed to find ovarian cancer cells.

In simpler terms, both therapies involve giving the body’s immune system a boost to help fight cancer more effectively. It’s like giving the immune system an upgraded set of tools to target and destroy cancer cells.

 

One of Europe’s Leading Start-up Hubs

Oslo Cancer Cluster Incubator made the Financial Times Europe’s Leading Start-up Hubs list.

“This recognition by the Financial Times celebrates our dedication to transforming oncology research and places us in a league with Europe’s most innovative ecosystems. It’s about more than accolades; it reflects our collective impact in pioneering new frontiers in cancer therapy and patient care,” said Ketil Widerberg, CEO of Oslo Cancer Cluster Incubator, when he was made aware of the news.

Ketil Widerberg, CEO of Oslo Cancer Cluster Incubator, is happy about making the Financial Times ranking. Photo: Fartein Rudjord

“This honor is a testament to the synergy between groundbreaking science and entrepreneurial spirit within the Oslo Cancer Cluster Incubator. Our unique approach, focusing on collaboration and support, sets us apart in Europe’s diverse and dynamic start-up landscape, as highlighted by the Financial Times.” Ketil Widerberg

Read more about the incubator companies and community on this incubator webpage.

Two Norwegian hubs

Only two Norwegian hubs are in the ranking. They are 6AM Accelerator, a pre-seed accelerator and investor for tech startups in Trondheim, and Oslo Cancer Cluster Incubator, with its laboratory-based community and cancer-focused companies next to Oslo University Hospital, the Radium Hospital. Oslo Cancer Cluster made 104th place out of 125 hubs in total.

Here you can read the complete list (link to Financial Times). 

It is also published as a Special Report in the Financial Times.

Specialized lab infrastructure

“With world-leading researchers in shared and individual labs Oslo Cancer Cluster Incubator exemplifies the critical role specialized lab infrastructure plays in supporting focused innovation within the incubator framework, particularly in the demanding field of cancer diagnostics and therapies,” said Janne Nestvold, COO of Oslo Cancer Cluster Incubator.

Woman in lab coat in lab

Janne Nestvold, COO of Oslo Cancer Cluster Incubator, in one of the incubator’s shared laboratories. Photo: Fartein Rudjord

Ranking methodology

According to Financial Times and their partners Statista and Sifted, Europe’s Leading Start-Up Hubs 2024 is a ranking of the top centres for founders offering incubator and/or accelerator programmes to people who want to build or grow a company.

To identify the 125 leading hubs, a registration and survey process was conducted. Several thousand hubs were evaluated, and several elements were considered for the evaluation, with the main criterion being the assessment of the respective start-up hub by alumni who participated in at least one incubator or accelerator programme run by the respective hub. In addition, the recommendations of external experts, such as investors, entrepreneurs, and academics were included. Finally, the most successful startups coming out of a hub were examined.

More about the ranking and methodology in this article in the Financial Times.

 

What does it take to make it?

What does it take to make it for new biotech companies? We are looking for answers, digging into the legacy and environment surrounding successful start-up companies like ARTBIO.

One of the newest members of Oslo Cancer Cluster is the clinical-stage radiopharmaceutical company ARTBIO. On their webpage, they present the company in these words:

ARTBIO is redefining cancer care by developing a new class of alpha radioligand therapies (ART) and building the ecosystem that maximizes their potential.

We first wrote about ARTBIO in an article presenting the newest members in January. Here, we can read that ARTBIO is shaped by a long-standing scientific legacy with nearly a century of pioneering work in radiation therapy conducted at the University of Oslo and Norway’s Radium Hospital.

What is this legacy all about, and what kind of environment is optimal for successful start-up companies like ARTBIO to grow up in?

The answer appears to be fourfold.

The obvious part: financing

Part of the answer for ARTBIO is the tremendous financing round that raised USD 90 Million in December last year, for progress in the pipeline and isotope technology development for a new class of alpha radioligand therapies. The news of the company raising this amount from private investors made headlines in the Norwegian newspaper E24. How was this possible in today’s slow and skeptical market?

“There are several reasons why we managed to raise one billion NOK in the series A investment. The first one is that ARTBIO is a very attractive investment case with a differentiated technology and pipeline within radio pharmacy, which is a field that is receiving a lot of attention internationally”, said Anders Tuv.

He is Managing Director at Radforsk, an early-stage evergreen fund dedicated to oncology. Radforsk is one of ARTBIO’s founders.

In the latest investment round Boston-based venture capital fund Third Rock Ventures was the main investor, together with an undisclosed healthcare fund and existing seed lead investors F-Prime Capital and Omega Funds, according to a press release from the company.

The crucial part: the right people

“Even though it is crucial to have the right technology as a foundation, it is a must to have the right people and teams. And on that note, we have hit the bull’s eye with ARTBIO”, Tuv said and added:

“The company has been rigged the right way to see it through and succeed with realizing their potential in a global competition.”

Tuv especially mentioned the hiring of ARTBIO CEO Emanuele Ostuni as a key success factor, who was also the first full-time employee. He is described as bright, tenacious, and with a compassionate drive to succeed for patients.

To the question what do you think it will take to get to the next milestone? Ostuni answered:

“Our goals all involve doing things that have not been done before. As such they require creativity, collaboration, and practical optimism.”

Ostuni added:

“We are working to start a phase 1 trial this year. That will require a working technology for P212 isolation and a robust process for manufacturing the therapeutic product. We are also working to create a broader pipeline of programs that addresses patient needs – several of these programs should also move forward this year.”

The historical part: the legacy

So far, we have touched upon the company’s technology, the people, and the financing. What about this long-standing scientific legacy that we started with?

Anders Tuv explained:

“The scientific founders behind ARTBIO are the same people that developed the only alpha-emitting radionuclide treatment on the market so far (Xofigo), the legendary researchers and founders Roy Larsen and Øyvind Bruland.”

Tuv added:

“I think that both the seed round and the series A round in particular have shown that we have worked hard and done many things right with ARTBIO. We got international specialist investors and founding CEO Emanuele involved at a very early stage with Roy Larsen and Øyvind Bruland, and F-Prime and Radforsk have been active investors, building the company and heavily involved from the beginning. We have been thinking globally from the start and extracted talent where they were to be found.”

This is the reason why ARTBIO has offices in Boston, Basel, London, and Oslo.

The part of the environment

Oslo Cancer Cluster Innovation Park and Incubator, and the entire Campus around the Radium Hospital, including Radforsk, offer an environment for companies like ARTBIO to begin their journey, especially in radiopharmacy and precision medicine in cancer.

“We have a strong legacy and a good ecosystem for radiopharmacy in Oslo, including the Radium Hospital and the environment in Oslo Cancer Cluster”, Tuv said, and Ostuni agreed:

“We appreciate the availability of flexible space that is already partially equipped at Oslo Cancer Cluster Incubator – it allowed us to get started quickly when we were building the company.”

“The culture of openness and support at the Radium hospital also made sure that we could establish collaborations with academic groups and progress some programs while at the same time providing educational opportunities for female scientists”, said Ostuni.

So there you have it; the somewhat complex answer to what it takes to make it – at least through the first serious financing rounds.

About ARTBIO and Radforsk

ARTBIO’s approach: Alpha radioligand therapeutics (ARTs) are gaining attention as a promising experimental modality for delivering lethal radioactivity directly to cancer cells. The unique ARTBIO approach selects the optimal alpha-precursor isotope (Pb-212) and tumour-specific targets to create therapeutics with the potential for the highest efficacy and safety. ARTBIO is currently advancing multiple pipeline programs with lead program AB001 first in human trials.

Radforsk is engaged in the commercialisation of cancer research. Our goal is to develop better cancer treatment – for all patients. We invest in and develop infrastructure through Radforsk Innovation and companies through Radforsk Invest. Radforsk Invest is an oncology focused investment fund dedicated to developing immunotherapies, precision medicine and radiopharmaceuticals. The fund has an evergreen structure allowing flexibility and focus on investments that will create long-term value. Radforsk Invest`s model is based on very active ownership as investors and hands-on company builders. Radforsk’s portfolio of companies spans from early start-ups to public companies with products on the global market. For more information, please contact Anders Tuv, Managing Director Radforsk Invest (at@radforsk.no).