Norwegian Ultimovacs has made some big announcements recently, including discussions for a fifth phase II clinical trial with universal cancer vaccine UV1, a private placement of 270 MNOK to fund the trial and other projects, plus the FDA’s decision to grant dual Fast Track designation for UV1 in advanced melanoma. To discuss this and more, Ultimovacs’ CEO Carlos de Sousa linked up to the BioStock Studio remotely from Oslo for a Q&A.
Watch the full interview with Carlos de Sousa below.
Norwegian Ultimovacs continues to expand its clinical development pipeline with universal cancer vaccine UV1. This week, the company announced its plan to initiate a fifth phase II trial with the candidate – a combination study with checkpoint inhibitor pembrolizumab in non-small cell lung cancer. The study will be conducted at 8-10 sites across Norway and led by principal investigator Professor Odd Terje Brustugun.
Biotech company Ultimovacs has a broad clinical pipeline aimed at developing a universal cancer vaccine. The company’s vision is to combine their vaccine, UV1, with other classes of immunotherapy, like checkpoint inhibitors (CPIs), to help give late-stage cancer patients extended survival times and remove or reduce the size of tumours.
Through this extensive programme, Ultimovacs is evaluating UV1 across a vast spectrum of cancer indications, including non-small cell lung cancer (NSCLC), metastatic malignant melanoma, ovarian cancer, head and neck squamous cell carcinoma and malignant pleural mesothelioma.
Fast Track awarded
Just recently, the company’s work with UV1 in advanced melanoma achieved a very significant milestone: dual Fast Track designation from the FDA. This decision may help pave the way for other regulatory benefits and will help motivate new clinical trials with UV1.
FDA’s Fast Track-decision was supported mainly by Ultimovac’s disclosure of positive results from their phase I trials in advanced melanoma, where UV1 was tested in combination with CPIs pembrolizumab (anti-PD-1, also known under the brand name Keytruda) and ipilimumab (anti-CTLA-4, also known under the brand name Yervoy), respectively.
A significant opportunity for Ultimovacs in NSCLC
CPIs, and pembrolizumab in particular, have become standard of care for many types of cancer, not just melanoma. For example, in NSCLC – a common type of cancer in both men and women – CPIs have a 56 per cent value share among all treatment options, according to Global Data, which corresponds to almost 12 BUSD in global value. Furthermore, pembrolizumab, specifically, is indicated as monotherapy treatment for NSCLC patients, where it represents a market share of roughly 67 per cent among all CPI options.
Across the US, EU5, Japan, and China, an estimated 850 000 new cases of NSCLC are diagnosed each year. Considering the very poor prognosis for patients with metastatic disease (the 5-year survival rate is around 7 per cent), and considering the extensive use of pembrolizumab as standard of care in NSCLC, Ultimovacs sees a significant opportunity. The company estimates that 33 per cent of the total NSCLC population is potentially eligible for a UV1/pembrolizumab combination treatment.
Phase II trial to be launched with UV1
Due to such vast market potential, Ultimovacs has announced the launch of the fifth clinical phase II trial with UV1, LUNGVAC, in NSCLC. This trial will investigate the safety and efficacy of UV1 in combination with pembrolizumab in NSCLC patients with advanced or metastatic disease. LUNGVAC will be a multi-centre, randomised, open-label trial treating patients with tumours classified within the adenocarcinoma or squamous subgroups of NSCLC and where patients have not previously received pembrolizumab treatment. The primary endpoint of the trial will be progression-free survival, while the secondary endpoints will include response rate and overall survival.
Ultimovacs’ CEO Carlos de Sousa had this to say about the trial in a press release:
»We see this new trial as a significant opportunity for Ultimovacs to make a difference to the lives of thousands of patients with advanced lung cancer. Our extensive phase II program is aimed at building a substantial evidence base that UV1 in combination with checkpoint inhibitors can stimulate the immune response resulting in enhanced treatment outcomes.«
Renowned PI heading clinical trial
Professor Odd Terje Brustugun, who is well respected within the field of oncology will be the principal investigator for the trial. The sponsor of the trial will be Drammen Hospital, a leading oncology research centre in Norway, and the study is expected to enrol approximately 138 patients and be conducted at 8-10 clinical centres across the country. The first patient is expected to be treated in H1 2022, with a data read-out from the trial anticipated by the end of 2024.
Professor Brustugun commented as well:
»NSCLC remains a major cause of premature death. Checkpoint inhibitors like pembrolizumab have changed the treatment landscape for lung cancer in advanced healthcare systems. The LUNGVAC trial will indicate whether the combination of UV1 with pembrolizumab can further improve the prospects for patients.«
Ultimovacs’ potential keeps growing
To fund the LUNGVAC trial, as well as other projects, Ultimovacs has just announced a Private Placement raising 270 MNOK. When LUNGVAC is initiated, Ultimovacs will be running a total of five phase II trials evaluating UV1 with more than 650 patients to be enrolled at close to 100 hospitals across 15 countries – an ambitious clinical footprint for such a small company.
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.
Copenhagen-based Evaxion Biotech runs several projects based on its proprietary AI drug discovery platform. The main candidate EVX-01 is developed as a combination therapy with checkpoint inhibitors. A phase IIb trial is planned to start this winter, in which EVX-01 will be combined with blockbuster drug Keytruda after a recent collaboration agreement between Evaxion and Merck & Co. subsidiary MSD.
Danish Evaxion Biotech has developed an AI platform to enable fast and effective discovery and development of immunotherapies and vaccines. Out of four ongoing development projects, two are currently being evaluated in clinical trials, where the main candidate EVX-01 is headed for phase IIb this winter.
EVX-01 is a patient-specific cancer neoepitope immunotherapy, developed for the treatment of metastatic melanoma. In a recent phase I/IIa study, EVX-01 showed an antitumour effect in most patients, with an objective response rate of 67 per cent when used in combination with a PD1 checkpoint inhibitor in metastatic melanoma. Two of the patients in the study, corresponding to 22 per cent of participants, achieved a complete response. Read more about the trial here.
Collaborating with Merck on the phase IIb study
The next step in the development of EVX-01 is a phase IIb study. Based on the phase I/IIa data reported on EVX-01, Evaxion Biotech entered into a collaboration agreement with MSD, a subsidiary of American pharmaceutical giant Merck & Co., for a collaboration on the clinical phase IIb trial. In the trial, EVX-01 is to be evaluated in combination with MSD’s blockbuster checkpoint inhibitor Keytruda, in patients with stage III and stage IV metastatic melanoma. In the collaboration, Evaxion Biotech will be responsible for conducting the study, and MSD will contribute with the Keytruda substance as well as support the data readout.
»We are extremely proud to collaborate with MSD, one of the world’s premier immuno-oncology companies, on our upcoming phase IIb trial with EVX-01. The promising phase I/IIa data, which we reported in July, showed that EVX-01 may be able to improve the treatment landscape in melanoma and potentially other cancers. Now that checkpoint inhibitors including Keytruda have become the standard of care for these patients, we are excited about the potential additive benefits of our drug candidate to further improve treatment and to strengthen the evidence supporting our platform and clinical pipeline. Furthermore, this collaboration will also reduce the cost of conducting our phase IIb trial on EVX-01.« —Lars Wegner, CEO Evaxion Biotech.
EVX-01 further enhances the effect of Keytruda
Keytruda is a checkpoint inhibitor used to treat several forms of cancer, for example melanoma, non-small cell lung cancer, bladder cancer and head and neck squamous cell cancer. The drug is one of the main pillars in Merck’s drug portfolio amounting to more than a third of the company´s total sales. In the second quarter of 2021 alone, Keytruda sold for 4.2 billion USD.
Keytruda targets the PD-1, a so-called checkpoint protein found on T-cells acting as a type of off switch, preventing T-cells from going into attack mode. While PD-1 can have beneficial effects by suppressing an immune response in, for example, autoimmune disease, in cancer, it helps cancer cells avoid the patient’s immune system. Therefore, Keytruda is called a checkpoint inhibitor, as it is introduced to dampen the effect of the PD-1 protein, enabling the T-cell attack on the cancer cells.
However, Keytruda alone does not always give a proper cancer specific immune response, therefore, by adding EVX-01 to the mix, Evaxion Biotech hopes to further help the immune system recognise the cancer cells, thus facilitating a better cancer specific immune response. A first sign of positive treatment effect of EVX-01 was shown in the phase I/IIa study, where the drug was combined with Keytruda or another checkpoint inhibitor. Now, the company hopes to get further Proof-of-Concept for the Keytruda combination in the upcoming phase IIb trial.
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.
For Sprint Bioscience the third quarter was an intense and news-dense period. Thanks to a licensing agreement and a rights issue, the company now finds itself in its strongest financial position to date and ready to take the next step in its development. BioStock contacted CEO Erik Kinnman to get his view on the past quarter and on the future.
With three outlicensed drug programs, with a combined potential value of 747 million USD, plus potential royalties, the future has a lot to offer Sprint Bioscience. The latest in the line of license deals is the immunooncology program Vps34. During the third quarter, the company worked intensely on handover to American Deciphera Pharmaceuticals, that is now taking over the helm in the program.
Solid base for continued investments
A brand new new license agreement and a completed rights issue mean that Sprint Bioscience stands at a cash position of 85.7 million SEK at the end of the third quarter, ready to invest further in new preclinical drug programs.
And the company has not been slow to make use of this. Shortly after Vps34 was outlicensed, the company announced the next addition to the internal development portfolio, NIMA. The goal of the project is to develop a treatment for solid cancerous tumours. The candidate aims to inhibit the tumour’s ability to program the microenvironment around it, thus preventing tumour growth and facilitating attacks from the immune system. You can read more about the program here.
Great interest in the development projects
In addition, progress has also been made in the DISA development program, where the intended target protein has been announced. In connection with this, the marketing of the program began, with intensified dialogues with potential licensees. A first stop on the marketing journey was the partnering conference BIO-Europe, which took place during the past week, where Sprint Bioscience was met with great interest in both DISA and other development programs.
In parallel with the escalating marketing of DISA, work is also ongoing to find new interesting starting points for more drug development programs. One such program is carried out in collaboration with Dr Julian Walfridsson at KarolinskaInstitutet, a program that was recently awarded a research grant of 2.5 million SEK from the Swedish Foundation forStrategic Research.Read more.
Björn Sjöstrand new Chairman of the Board
However, it was not only the coffers and portfolio that expanded during the quarter, Sprint Bioscience also took steps to strengthen the organisation. The company has appointed a new CFO in the form of Mattias Skalmstad and the board was joined by life science entrepreneur Björn Sjöstrand as its new chairman. You can read an interview with Sjöstrand where he talks about his entry into, and his view of, the company here.
CEO comments
Overall, it has been an eventful quarter for Sprint Bioscience. BioStock contacted the company’s CEO Erik Kinnman to get his view of the third quarter and to learn more about what he sees ahead as we move towards winter.
First of all, Erik, how would you like to sum up the past quarter?
– It’s been very intense and successful. We have outlicensed the VPS34 program to Deciphera Pharmaceuticals, a very strong partner that has already shown great commitment to taking the program further. This is our largest deal to date and together with the new share issue carried out in August, this means that we have greatly strengthened our financial position.
– With a strong financial position in place, we can look to the future and focus on continuing to develop the business and build values in both outlicensed and internal programs.
BIO-Europe was held this week, an important event for you where you had conversations about the DISA project. What is the interest in the project so far?
– There is a noticeable interest from a large number of different companies. Some are interested more generally in what we have to offer, others are more specifically interested in either the VADA or DISA programs. It is clear that the mechanisms we address are highly interesting. DISA is in the relatively early stages compared to the VADA programme and we have received valuable feedback and started new dialogues. The BIO-Europe meeting has been successful for us and provided us with good support for continued discussions and marketing of our pharmaceutical programs.
Looking ahead, what milestones do you see in the next year?
– We continue to work intensively with our partners and the outlicensed programs to reach the next milestone on the path to clinical development and market approval. Such successes will further validate our business model. Furthermore, we want to continue to build our internal portfolio of highly interesting cancer drug programs and we are constantly working to sign new licensing agreements with strong international partners.
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.
For Danish DanCann Pharma, Thursday brought good news from its partner Canadian Tetra Bio-Pharma. In May, the two companies signed an exclusive distribution deal regarding three of Tetra Bio-Pharma’s products. Last week, the EMA Committee for Orphan Medicinal Products issued a positive opinion on Tetra Bio-Pharma’s cannabinoid-based drug targeting neuropathic pain. BioStock reached out to DanCann Pharma’s CEO Jeppe Krog Rasmussen for a comment on the possible implications of the positive opinion.
On February 25, Danish biotech DanCann Pharma signed a letter of intent (LOI) with Canadian Tetra Bio-Pharma Inc for exclusive distribution of the cannabinoid-based drugs Reduvo Adversa and Qixleef in Denmark, Norway, Sweden, Finland, and Germany. The agreement also covers Tetra’s over-the-counter product Enjouca. The parties went on to sign a definitive distribution agreement on May 5.
Reduvo Adversa (dronabinol using a new route of administration in the form of mucoadhesive tablets) is intended for the treatment of CINV patients (chemotherapy-induced nausea and vomiting) and for AIDS-related anorexia associated with weight loss. Qixleef and Enjouca are intended for the treatment of uncontrolled pain in patients with advanced cancer and for breakthrough pain.
Qixleef is a botanical inhaled drug product with a fixed ratio of THC and CBD that meets USA cGMP regulatory requirements. According to the manufacturer, it provides fast-acting relief from pain and offers patients a viable and non-opioid alternative for pain management.
Positive Opinion for Orphan Drug Designation from EMA
Last week, the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) issued a positive opinion on Tetra-Bio Pharma’s application for Orphan Drug Designation (ODD) for Qixleff as a potential treatment for Complex Regional Pain Syndrome (CRPS), a chronic neuropathic pain condition.
If granted in Europe, it would represent Qixleef’s second ODD as a potential treatment for CRPS, in addition to the ODD granted by the U.S. FDA in March 2018. The positive opinion issued by the COMP will be sent to the European Commission, which is expected to grant the orphan designation within 30 days.
DanCann Pharma’s CEO comments
BioStock reached out to DanCann Pharma’s CEO Jeppe Krog Rasmussen for his take on the possible implications of the upcoming ODD approval in the EU.
Jeppe, what will the ODD mean for the upcoming market introduction in Europe?
– The ODD designation is very positive news as it gives regulatory advantages during the development process. Importantly, it can lead to market exclusivity, i.e., no direct competition from generic therapies for 10 years in the EU (7 years in the US), after market launch. In addition, an ODD also entails reduced drug development costs and regulatory fees as well as administrative and procedural assistance. On top of this, the review process will be accelerated. In sum, the ODD gives Tetra-Bio a competitive edge and a head start in gaining market shares.
– This, in turn, will of course also affect DanCann Pharma in a very direct and positive way as, which you mentioned, we have signed an exclusive distribution agreement for Denmark, Norway, Sweden, Finland, and Germany. The sooner the drug reaches the market, the sooner it will have a directly financial effect on DanCann Pharma.
How big is the market for treating Complex Regional Pain Syndrome (CRPS)?
– CRPS affects only 4,4 individuals out of 10,000 in Europe, which is part of why the EMA recommends granting the candidate an ODD. Given that today’s treatments are suboptimal in terms of pain relief, there is market space for Qixleef, a treatment that can provide analgesic effect, improve sleep, reduce anxiety and depression as well as relieve pain. Both we and Tetra-Bio Pharma are convinced that the candidate, upon approval, will be a safe and effective treatment alternative for pain management and a better alternative than opioids.
– Also, it is worth pointing out, that a single decision from the European Commission will be valid in all EU member states upon market approval. That means that Qixleef would be simultaneously approved in Denmark, Norway, Sweden, Finland, and Germany, where DanCann have exclusive distribution rights.
To wrap this up, can you give our readers a status update of what’s on the agenda for DanCann Pharma now, and what milestones you hope to reach in the coming months?
– Followings last week’s closing on the acquisition of CannGros we are working on the integration of the company into DanCann Pharma, with extended focus on the ongoing process around our product application for another product in the form of a cannabis extract in an oil solution.
– Furthermore, we are performing a lot of training processes to maximize the output of the ongoing preliminary operations in Biotech Pharm1, awaiting final approval in the new year. We expect to apply for our application for the EU-GMP certificate in Biotech Pharm1 very soon (within a few weeks) at the Danish Medicines Agency.
– From a strategic point of view, we have commenced with designing the next step for the company, looking towards new goals, developing, and materializing the strategy that will glue the current DanCann Pharma together with CannGros. Setting standards for activities in our future downstream processes.
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.
Earlier this autumn, Abliva announced that NV354, the company’s second candidate within the primary mitochondrial disease space, will progress to clinical phase. NV354 is initially being developed for the fatal Leigh syndrome, a disease that usually debuts before the age of 2 and patients often die before the age of 5. With NV354 about to join Abliva’s leading candidate against primary mitochondrial disease, KL1333, in clinical development, BioStock takes a closer look at the candidate.
Primary mitochondrial diseases may be rare, but their impact on patients is profound. Lund-based Abliva has made it their mission to develop treatments that can improve the lives of these patients and are currently developing two candidates, KL1333 and NV354.
Primary mitochondrial diseases
Starting with the basics, what is a primary mitochondrial disease? In short, the term encompasses a group of diseases caused by genetic mutations leading to poorly functioning mitochondria, which leads to a range of debilitating symptoms. As the mitochondria are responsible for the body’s energy production, some of these symptoms can be very severe, such as difficulties breathing and moving.
Leigh syndrome – a neurological syndrome
One mitochondrial disease that causes severe symptoms leading to early death in children is Leigh syndrome, named after British neuropsychiatrist Archibald Denis Leigh, the first to describe the syndrome in the early 1950s. This neurological syndrome is characterised by changes in the brain and early symptoms include recurrent vomiting and movement disorders. Later, symptoms such as breathing difficulties can emerge.
Poor prognosis and no treatment
Whilst Leigh syndrome is very rare, according to the Swedish National Board of Health and Welfare it affects 2-3 children in Sweden per year, it takes a heavy toll on mainly young children. In most cases the disease debuts early, already before the age of 2, and, for the majority of sufferers, sadly, the prognosis is extremely poor. Most of the affected children die before the age of 5 and there are currently no treatments available.
NV354 restores energy production
With NV354, Abliva is aiming to fix a fundamental problem in Leigh syndrome and other mitochondrial diseases – energy conversion. Leigh syndrome is typically caused by what is known as Complex I dysfunction – a malfunctioning of the first of five protein complexes in the mitochondria that leads to poor energy conversion. Abliva’s NV354 is aimed at restoring energy production by functioning as an energy replacement, through succinate, an energy substrate already present in the human body.
NV354 shows promise
Abliva has several reasons to feel satisfied about the ongoing development of NV354. Not only is NV354 and its mechanism of action a product of research conducted by members of Abliva’s own research team, it has also shown promising preclinical results. In September, Abliva presented the preclinical documentation regarding NV354 to the British regulatory authority, the MHRA, who confirmed with Abliva that the preclinical package supports dosing in human subjects. Following this meeting, Abliva will now advance NV354 to clinical studies with the aim of initiating a phase I study in 2022.
Finally, it is worth noting that the company believes that NV354 has potential beyond Leigh syndrome. Abliva has mentioned two other mitochondrial diseases, MELAS and LHON, as indications where NV354 could be used and potentially help make a difference to patients who today lack treatment options.
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.
After complying with the conditions given by the Danish Ethics committee in September, Nordic biotech Coegin Pharma has received the final approval for initiating the phase I/II COAK study in actinic keratosis patients. From the beginning of November, the company will begin patient recruitment, and thus take an important step towards developing a novel treatment for a disease with a large unmet medical need.
Cancer on its own is one of the leading causes of death, globally. However, putting additional pressure on healthcare systems are pre-cancerous diseases, of which there is still a distinct lack of awareness. One example is actinic keratosis (AK), a pre-cancerous condition of the skin. AK skin lesions are a sign of chronic inflammation caused by high exposure to harmful UV rays from the sun, and, if left untreated, they can develop into more serious diseases including squamous cell carcinoma (SCC), a cancer of the skin that is potentially life-threatening.
The lack of awareness around AK leads to a heavy burden on patients who ignore these lesions until it is too late and become cancerous. Meanwhile, the most common treatment for the condition is cryotherapy – a freezing off of the lesion through liquid nitrogen that can lead to scarring, blisters, or other permanent changes to the skin. Therefore,new innovative therapies are in high demand.
Coegin Pharma address AK
A biopharma company addressing this challenge is Coegin Pharma, with a business model based on efficient development of new drug candidates for diseases with an urgent medical need where the cPLA₂α enzyme is central to disease progression. This includes AK. Thus, through several years of well-validated research, the cPLA₂α enzyme has become a therapeutic target for the company, and AVX001 was developed as a compound able to block cPLA₂α, thus becoming the company’s lead candidate for actinic keratosis and skin cancer.
Read more about the company’s background and vision here.
Planning for the COAK study
The company has been planning a combined phase I/II trial with AVX001 in AK called the Copenhagen Actinic Keratosis Study (COAK study). One of the most important steps to prepare for this trial has been partnering with the virtual CRO Studies&Me – the first virtual CRO in Europe.
Thanks to the collaboration with Studies&Me, the COAK clinical trial will be conducted with a decentralised approach, which is based on digital tools designed to put the patients front and centre. The patients will receive guidance and support, and they will be able to report back to the hospital from the comfort of their homes, reducing the number of physical visits to the hospital.
Read more about the collaboration in this in-depth joint BioStock Q&A with Coegin Pharma’s CEO Tore Duvold and Studies&Me’s CEO John Zibert.
Approval from the Danish Authorities
Earlier this year, Coegin filed for approval to initiate COAK from the Danish authorities. The Medicines Agency in Denmark gave its approval earlier this summer, however the company still required the approval from the Ethics Committee before it could begin the study.
A conditional approval from the Ethics Committee arrived in September. This approval entailed that Coegin would need to make small adjustments to patient information. BioStock was able to get in touch with Tore Duvold, who answered some questions about the meaning of the conditional approval. Read more here.
After complying with the conditions given by the Ethics Committee, the company has now announced receiving full approval and thus has the official green light to initiate the study.
Details of the study
The company expects COAK to present top-line results towards the end of Q1, 2022. The study will include at least sixty patients divided into three groups receiving two different strengths of AVX001 or placebo in the form of a cosmetically attractive gel formulation. The patients will be administering the treatment themselves once daily for four weeks and will be assessed up to eight weeks after end of treatment. The primary endpoints are safety and tolerability, and the secondary endpoints are efficacy and quality of life.
The COAK trial will be conducted at Bispebjerg Hospital by lead investigator Professor Merete Hædersdal, who answered some questions about the trial and the overall clinical development of AVX001 in a recent BioStock interview.
Exciting time for Coegin
Overall, this is a very important step for the company and its vision of potentially introducing a novel treatment for patients suffering from pre-cancerous conditions like AK and other diseases where the cPLA₂α enzyme plays a key role, such as some forms of cancer as well as chronic inflammatory diseases like arthritis and fibrosis.
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.
Recently, gene therapy company CombiGene signed an exclusive global license agreement for their gene therapy candidate CG01 with Spark Therapeutics. The deal is potentially worth $328.5 million excluding royalties. Much has happened since CombiGene was formed and BioStock turned to the scientific founders Professor Merab Kokaia and Associate Professor David Woldbye, for a comment on the company’s development.
The foundation of CombiGene was laid over ten years ago. Prior to this, preclinical research had suggested that the production of neuropeptide Y (NPY) increases in the brain after an epileptic seizure. Professor Merab Kokaia, working at the Epilepsy Center at LundUniversity and Associate Professor David Woldbye, Department of Neuroscience at the University of Copenhagen, initiated a research collaboration across the strait, with the aim ofdeveloping new treatments for hard-to-treat epilepsy. The hypothesis was based on the assumption that NPY inhibits epileptic seizures, as a part of the body’s own defenses. Since then, this assumption has been confirmed in several studies.
A challenge to administer drugs to the brain
The researchers soon realised that by combining the neurotransmitter NPY with its receptor Y2, a better effect should be achieved, especially if the drug could exclusively target the area of the brain where the epileptic attack is being triggered. Now it was a question of developing a method of administering the drug to the brain. This is a challenge due to the blood-brain barrier that protects the brain, but at the same time constitutes an obstacle to the transportation of drugs to the brain.
The solution was to use a harmless, non-pathogenic virus whose own DNA was largely removed and replaced with functional DNA sequences of NPY and Y2 (AAV vectors) for injection directly into the damaged area of the brain. Thus, CombiGene’s gene therapy project with the candidate CG01 was born.
The culmination of a long development cycle
On October 12, 2021, CombiGene announced that it had entered into an exclusive collaboration and licensing agreement for the CG01 project with Spark Therapeutics, a gene therapy company that is part of the RocheGroup. The deal amounts to 328.5 million USD excluding royalties. By Swedish standards it is a very substantial deal that Medicon Village-based CombiGene, a small company with limited internal resources, has signed with one of the biggest players in the industry.
Extensive work now remains in order to carry the CG01 project through the upcoming clinical studies together with Spark.
High price tag for exclusive rights
The agreement gives Spark the exclusive global right to develop, manufacture, and commercialise CG01. CombiGene will continue to conduct certain parts of the preclinical program in collaboration with Spark.
Under the terms of the agreement, CombiGene is eligible to receive up to 328.5 million USD excluding royalties of 8.5 million USD at the time of signing, and up to 50 million USD at preclinical and clinical milestones. CombiGene will also be reimbursed for agreed development costs. At the point of commercialisation, CombiGene is eligible for incremental royalties up to low double-digit percentages based on net sales.
Comment from the founders
BioStock reached out to CombiGene’s scientific founders, Professor Merab Kokaia and Associate Professor David Woldbye, for a comment.
After the agreement with Spark, it only feels right to start with the classic sports question, how do you feel?
“It feels great. Both us researchers and the team at CombiGene have put a lot of time and energy into getting to the point where clinical studies are possible so the agreement with Spark could not have come at a better time. Spark has the financial and intellectual resources to conduct the clinical studies with CG01 in patients with intractable epilepsy. Despite treatment with today’s medications, these patients suffer from uncontrolled epileptic seizures. If CG01 shows positive results in clinical studies, it represents a completely unique treatment option that can help these patients and significantly improve their quality of life.
“This is a great day for CombiGene and for me and Prof Kokaia”, says Assoc Prof Woldbye. “This is the culmination of preclinical work, dating as far back as 1996, showing that neuropeptide Y exerts seizure-suppressant effects. Through the deal with Spark, we now have ensured that this treatment can be tested in the clinic for temporal lobe epilepsy patients. Since many of these patients are drug resistant, there is a great need for developing novel treatments. It is my hope that with this deal, we can now get a great chance to help these patients”.
The deal is a clear sign of how Spark value the potential of CG01. How would you describe your hopes for further development, based on the data you have accumulated over the years?
– We have been working on the NPY/Y2 gene therapy project for many years and we have demonstrated – in various animal models as well as in human brain tissue from epilepsy patients – that it works and suppresses seizures. So, I am very optimistic that it will work in humans as well, but of course that remains to be seen. The agreement with Spark ensures that the clinical studies that will give us answers regarding what effect CG01 has on drug-resistant focal epilepsy, will be carried out.
”If we, in collaboration with Spark, can show that CombiGene’s gene therapy candidate works in a planned human drug-resistant epilepsy trial, it is my hope and prediction that this will pave the way for the use of gene therapy in other epilepsy patients as well. The reasoning behind this belief is that gene therapy has the potential to selectively treat the part of the brain where the seizure is located and may therefore also reduce the use of antiseizure drugs. In turn, that would also reduce the potential side effects of taking such drugs for extended periods of a patient’s life”, says Assoc Prof David Woldbye.
Finally, will you have close contacts with the research cluster behind Spark for the further development of CG01?
So far, we have had very good contact and discussions with the Spark team, and I am impressed by their knowledge and experience in the field of gene therapy. So, I am very positive about the future collaboration with Spark and hope for continued successful development of the CG01 project with the combined strengths from CombiGene and Spark.
Assoc Prof Woldbye adds “Yes, it is part of the deal between CombiGene and Spark that Prof. Kokaia and I will continue to be involved in driving the project forward together with Spark. Since this project is like a child to me and Prof Kokaia, we will be happy to maintain a role in the project in the future interaction with the very competent Spark team.”
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.
Early detection and diagnostics of cancer is one of the best tools for combating what remains one of the world’s deadliest diseases. Swedish medtech company BibbInstruments develops the EndoDrill Model X, a medical device with the potential to make a significant dent in the cancer diagnostics industry while addressing a market potentially worth close to 1 billion USD, according to the company.
Despite the advancements made in cancer therapeutics over the last decade, cancer remains one of the leading causes of death world-wide. According to data published in Our World in Data, around 10 million people die from cancer each year. One of the biggest challenges in cancer treatment is early detection and diagnostics. Many cancers become fatal because they are caught too late, and this is due, in large part, to a lack of effective diagnostics tools.
Endoscopic ultrasound (EUS) is a relatively new examination tool. It is a minimally invasive procedure to assess gastrointestinal and lung diseases. Thanks to ultrasound guidance, representative samples can be taken safely, without harming the surrounding tissue. These samples are taken with a fine needle, either through fine needle aspiration (EUS-FNA, cytological sample) or biopsy (EUS-FNB, histological sample).
BibbInstruments redefines EUS diagnostics
EUS is the fastest growing endoscopic procedure, especially in the US. However, the failed detection rate of devices currently used in the clinic continues to be too high. The Lund-based medtech BiBBInstruments are addressing the issue with their EndoDrill Model X, the first CE-marked electric endoscopic biopsy device. The device can provide better tumour samples thank to its sampling method based on core needle biopsy (CNB) instead of FNA or FNB.
The benefits of the shift from FNB to CNB have already been observed in breast and prostate cancer. The method has become the gold standard in diagnosis of those indications, and it has been shown to give a more complete and accurate cancer diagnosis, leading to earlier treatment of patients afflicted by these serious cancers. The EndoDrill Model X is the first biopsy instruments that offers the same opportunity in endoscopic ultrasound-guided biopsy sampling.
Read a more in-depth overview of the company, which includes a link to a video showing how EndoDrill Model X works, here.
Broad market potential
EndoDrill Model X’s market potential is significant, especially considering that EUS is the fastest growing endoscopic segment, and there are constantly new applications for diagnosis, staging and treatment.
According to the company, the device could be used for detecting 8 of the top 15 deadliest cancers. This includes the deadliest form of cancer, lung cancer, which is responsible for almost 2 million deaths worldwide each year. Furthermore, the company estimates that more than 1 million biopsy procedures are performed each year with EUS fine-needle instruments, constituting a global multi-million Euro market.
With those numbers in mind, BibbInstruments estimates that EndoDrill Model X has a market opportunity of 8.2 billion SEK, or close to 1 billion USD.
Two ongoing clinical validation studies
For now, the company is running two clinical validation studies with the Model X – EDMX01, for stomach tumours, and EDUX02, a pilot study in patients with suspected muscle invasive bladder cancer.
EDMX01, conducted at three Swedish university hospitals and including 20 patients, is aimed at validating EndoDrill Model X for stomach tumours by taking comparative samples from each patient with both EndoDrill Model X and the leading competing fine needle biopsy instrument.
Meanwhile, EDUX02 is run by a university hospital in Sweden and includes 10 patients. A follow-up effect study is already planned and reviewed by regulatory authorities provided that the pilot study goes according to plan.
A significant opportunity with EDUX02
The EUS market is dominated by some of the world’s largest medtech companies, e.g., Medtronic, Boston Scientific, Cook Medical and Olympus Medical. These are the strongest competitors to BibbInstruments when it comes to the gastrointestinal and respiratory tract EUS market.
However, BibbInstruments’ pilot clinical trial EDUX02represents a significant opportunity within bladder cancer, the fourth most common form of cancer in men and a disease where survival rates have remained unchanged over the last thirty years.
Bladder cancer is the only endoscopic indication where tissue biopsies are not normally taken at the initial endoscopic examination, and there are currently no marketed products designed for this purpose within this indication. Muscle invasive bladder cancer would be the first non-EUS market opportunity for the EndoDrill Model X, and the device would have no competition, as things stand now. Read more about the EDUX02 trial here.
BibbInstruments believes strongly that a successful clinical program could pave the way for a possible paradigm shift for the diagnosis of muscle invasive bladder cancer.
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.
It is time for 2021’s edition of the largest partnering meeting in the life science space – BIO-Europe. This week, representatives from nearly 1,500 companies will gather to establish new contacts as well as continue initiated discussions with potential partners, licensees and investors. BioStock hasspokentotheCEOsfromeight Swedish lifesciencecompanies–withvarying pipelinesatdifferent stagesofdevelopment–tolearn about theirexpectationsattheevent,given each of theiruniquesituations.
The 27th edition of BIO-Europe, organised by EBD Group, takes place on 25-28 October. In addition to one-on-one meetings, the partnering conference offers a variation of seminars and company presentations.
Partnership potential
With 2550 eager participants from over 50 countries, there is a good chance that BIO-Europe will lead to several partnerships between the participating players. For many smaller pharmaceutical and biotechnology companies, partnership with a larger pharma company is a necessity to ensure the resources and competence required to take a product through the final stages of development and market launch.
BioStock contacted eight Swedish life science companies – all at different stages of development and with varying portfolios – to learn about their goals with their planned partnering discussions during the conference.
Idogen
Idogen is on the verge of entering the clinical phase of development with its drug candidate IDO8 in haemophilia A.In addition, the company is developing IDOT for the treatment of organ rejection in kidney transplantation and IDO AID for autoimmune diseases, both in preclinical development.
– We are in a very exciting phase, where we are on our way from preclinic to clinical studies. This means that there is high interest among companies that are potential future partners for Idogen. Our intention is to meet said companies, deepen our relationships with them and share information on Idogen’s status and undertakings.
– The interest in our platform for tolerogenic cell therapy is increasing now that we can share new information and data. We will update potential partners on the plans for our upcoming clinical programme. Starting a clinical study with IDO 8, and treating the first patients, will generate proof-of-concept both for the first indication and for the technology as a whole.
– The first clinical study will include patients with severe haemophilia A who have developed antibodies against, and thus resistance towards, conventional treatment with coagulation factor VIII (FVIII). If we are able to show a positive treatment effect in this patient group – who present a high medical need – this would increase interest in other potential indications that our technology platform can be applied to, i.e. diseases characterised by unwanted activation of the immune system. This week, we have several intriguing meetings with large pharmaceutical companies.
RhoVac
RhoVac has recently hired StifelNicolausEuropeLimited as financial advisor. Their assignment comes in the form of assisting RhoVac in reaching a transaction or partnership deal for the cancer vaccine RV001 in the near future. The candidate, developed to prevent progression and metastases in prostate cancer, is currently being evaluated in a phase IIb study (BRaVac).
Anders Månsson, CEO RhoVac
CEOAndersMånsson,howdoesyourcollaborationwithStifelaffectwhat type meetingsyouplanduringthe conference,andwhatoutcomeyouexpectfromthem?
– Our agreement with Stifel means – during BIO-Europe as well as during all partnering conferences and meetings going forward – that we work together to ensure that we are in contact with all suitable and willing potential partners well in advance of the release of the BRaVac results, which are expected in the first half of next year.
Iconovo
Iconovo develops complete inhalation products, i.e. both inhalers and the associated drug formulations. For them, partnership and out-licensing are an important part of the company’s business model, and they already have several licensing agreements for three of the company’s four inhalation platforms.
Johan Wäborg, CEO Iconovo
CEOJohanWäborg,isthepurposeofyourparticipationatBIO-Europetohighlightyourfourthandnewest inhalationplatform,ICOpre,orareyoulooking for additionalagreementsfortheentireportfolio?
– We will have some discussions regarding ICOpre as an inhaler for upcoming generic inhalation products at BIO-Europe, but the main aim is to find customers who need innovative inhalation products. ICOpre can also be used for inhalation of new molecules, but we are mainly looking for customers who have an interest in our disposable inhaler ICOone.
– Furthermore, we will examine the interest for ICOone Nasal, as we are currently seeing a great demand for nasal powder inhalers. We are looking for customers with new drugs that would benefit from inhaled administration to favour a local effect in the lung or nose, to enable a rapid onset, or to replace injections with a more stable drug delivery.
Cyxone
Cyxone is attending Bio-Europe where the main focus is to find a strategic partner with the experience and resources to develop and commercialise Rabeximod in rheumatoid arthritis. In parallel, Cyxone is finalising the analysis of the data from a Covid-19 trial which was concluded in July and may, provided positive results from the study and market demand, continue to develop and commercialise Rabeximod in Covid-19.
Tara Heitner, CEO Cyxone
Tara Heitner, CEO, what expectations do you have on the interest for Rabeximod during the conference?
– We have been in discussion with many interested pharma companies in different geographic regions and we are in close discussions with a few interested candidates. We seek to continue these ongoing discussions to take them to the next level while reaching out to new interested parties.
– As we are getting closer to start of trial and the trial protocol has been fine-tuned, the CRO selection process is close to final and the required team is on board, so we are in an ideal position to further our discussions with the relevant parties. We are also expanding our outreach as the recent news on the safety concerns with JAK inhibitors means there is an even greater need for an oral drug with a novel mode of action which can treat the cellular basis of the disease and prevent progression and joint damage.
Immunicum
Immunotherapy company Immunicumhas a broad treatment focus in cancer with immune primer ilixadencel and cancer relapse vaccine DCP-001 at the forefront (both in phase II).
Erik Manting, CEO Immunicum
CEO Erik Manting, how do you intend to profile your broad clinical pipeline when discussing with potential partners during BIO-Europe?
– Immunicum is addressing difficult-to-treat established tumours and tumour recurrence, which we believe represent the biggest challenges for today’s cancer therapy. Our novel therapeutic approaches are based on off-the-shelf, intratumoural immune priming and relapse vaccination, with products showing promising efficacy in solid and blood-borne tumours, combined with an excellent safety profile.
– We have a rich, advanced pipeline with multiple ongoing clinical studies and upcoming clinical milestones to support our competitive clinical development strategy. In addition, Immunicum has developed a broad collaboration network with academia and other companies and is always on the look-out to develop new, differentiated therapeutics approaches and innovative combinations with other therapies, such as CAR T-cells.
Aptahem
Aptahem is approaching the first clinical studies with its lead candidate, Apta-1, developed as an emergency drug targeting sepsis, a condition that affects 49 million people annually, 11 million of which die. According to preclinical data, Apta-1 could potentially counteract the harmful effects that arise from sepsis.
Mikael Lindstam, CEO Aptahem
CEOMikael Lindstam, this is not the first time you have participated in BIO-Europe. Are your partnering goals different now that you have more preclinical data to back up your case?
– Yes, our broader dataset has a pretty big impact on how we go about the partnering event.
– Preclinical toxicology studies have been completed without any negative findings and we are awaiting the final report, we are starting GMP production, we have good results from our partners in academia and our commercial arrangements, and we have also started discussions for clinical studies.
– But above all, we have identified one of Apta-1’s mechanisms. This is an important milestone for us that will open doors to regulatory clarity and be value-enhancing in discussions with pharma companies as we can now describe ourmechanism, in a very important target, in a well-defined way.
BioInvent
BioInvent already has a number of licensing agreements and ongoing research collaborations with several leading pharmaceutical companies regarding the company’s immunomodulatory antibodies for cancer therapy. In addition, the company has its own development platform and produces antibodies both for themselves and other companies.
Martin Welschof, CEO BioInvent
BioInvent have entered into collaborations with reputable big pharma such as Pfizer and Merck. CEO Martin Welschof, do you have a similar agenda for your visit to BIO-Europe?
– We are pursuing an active business development strategy and are discussing with potential partners on a continuous basis. Currently we are evaluating potential geography-based partnerships that would add value to our development programs while still retaining significant upside for BioInvent. Such as the ongoing partnership with CASI Pharmaceuticals, Inc. for our lead compound BI-1206.
Sprint Bioscience
The preclinical development specialist SprintBioscience is a frequent visitor to BIO-Europe and has several licensing deals on its resumé. This year, in addition to the VADA project, the company is focused on communicating steps taken within the latest project, DISA, which aims to activate the immune system to target cancer and can be combined with immuno-oncology therapy, radiotherapy and chemotherapy.
Erik Kinnman, CEO Sprint Bioscience
CEOErikKinnman,overtheyearsyouhaveparticipatedatBIO-Europeonatleast20occasions,andhave validatedyourbusinessmodelby concluding severallicenseagreements.Whatsignificancewouldyousay thatthiseventhasforasmalldevelopmentcompanyandwhat will characterise yourparticipationthisyear, comparedtowhenyoufirstparticipated?
– BIO-Europe creates many opportunities to meet new potential licensees to our programs in a short period of timeand follow up with previous contacts. In short, it is an event that is extremely important for building networks. Our meetings there become entrances to deeper discussions and the time after an event like BIO-Europe is always extra intense. Positioning a company and building a network requires stubbornness and intense commitment, and the first few times we participated, our business development team really got to work hard to establish contacts.
– Today, we barely have time to log into the conference’s partnering system that we immediately receive meetingrequests, mainly thanks to our extensive network and track record of closing license agreements. Although the BIO-Europe conferences have been digital for a long time, our business development team has been able to conductmany meetings. Instead, the challenge comes from the fact that they are spread out over the day because the participants are in different time zones. This year we are participating with two programs and, as before, we focus onthe partnering part of the conference and meetings with our potential licensees.
BIO-Europe–amust-attendpartneringevent
One thing that all aformentioned companies have in common is that, despite different pipelines and stages ofdevelopment, they see BIO-Europe as a very important opportunity to build a network and develop relationships withother life science actors. Whether a company is looking for a partner to further develop its product, or hoping to find ataker for a project, or perhaps sell its products/services, BIO-Europe seems to be the perfect venue, an event with the potential to put wind in the sails of all participating players.
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.
