Medivir optimizes study design after meeting FDA

26 April, 2024

Medivir optimerar studiedesignen efter möte med FDA

Medivir has held another meeting with the FDA concerning the upcoming global phase IIb study, in which the company’s drug candidate, fostrox, will be evaluated in combination with Lenvima in liver cancer patients. The aim is to initiate the study in the US by early 2025.
– We have great momentum in the development program with fostrox right now, says Medivir’s CEO Jens Lindberg.

Medivir is developing the drug candidate fostrox (fostroxacitabine bralpamide) for the treatment of primary liver cancer, hepatocellular carcinoma (HCC) – the fifth most common form of cancer and the third most common cause of cancer death worldwide.

The goal is to establish fostrox as the first approved option when the standard treatment, Tecentriq/Avastin, is ineffective or not tolerated. Foxstrox has Orphan Drug Designation for the treatment of HCC in the US and Europe.

Clinical trials reveal sustained patient advantages

The company is assessing the candidate’s safety and tolerance in a fully enrolled phase Ib/IIa study combined with the cancer drug Lenvima. In late 2023, findings from the 18 patients with a minimum of 12 weeks of follow-up indicated enduring patient benefits, which become more pronounced with prolonged treatment duration.

The goal is to conduct a phase IIb study and obtain accelerated approval from the US Food and Drug Administration (FDA), which would mean a shorter time to market approval.

Type C meeting held with FDA

Last autumn, Medivir held a Type D meeting with the FDA, which was positive regarding critical parts of the design for the planned global phase IIb study. The next step, a Type C meeting, has now been held with the FDA, which resulted in an optimized study design for the upcoming study.

In summary, Medivir plans to use an improved capsule formulation of fostrox. Therefore, an initial dose run-in is required as part of the study, with additional patients and a lower dose to strengthen the study design.

Furthermore, the primary endpoint will be changed to Objective Response Rate (ORR), an accepted surrogate endpoint for survival, with secondary endpoints such as duration of response, progression-free survival, and overall survival. According to the company, ORR has supported accelerated approvals in previous HCC studies.

Progress with MIV-711

In addition to the positive interactions with the FDA regarding fostrox, Medivir has also made significant progress with the candidate MIV-711.The FDA has granted MIV-711 both Rare Pediatric Disease Designation (RPDD) and Orphan Drug Designation (ODD) for the treatment of Legg-Calvé-Perthes disease (LCPD).

Securing RPDD and ODD offers numerous regulatory incentives and advantages that can prove pivotal in advancing treatments for rare pediatric diseases.

BioStock will get back with a separate interview with the company regarding these regulatory advancements.

Comments from the CEO

BioStock reached out to Medivir’s CEO Jens Lindberg for a comment on the Type C meeting with the FDA and how the changed study design could potentially increase the chances of success.

Jens, could you provide some additional context behind the new study design you’ve recently adopted?

– The most important is that the changes we are making after the dialogue with the FDA partly strengthen the study design and thus the results that the study will show, but equally important is that our original plan and purpose for the study remains as before and that the size and timing are in line with the previously communicated plan. For example, one of the advantages of ORR as a primary endpoint is that it can be read out faster/earlier than progression-free survival.

Can you briefly explain how you relate to the FDA’s Project Optimus, which seeks to reform dose optimization and selection for oncology drug development?

– The FDA’s Project Optimus is a project that aims to enable companies in drug development to identify a so-called minimally effective dose. In the development work with fostrox, we have previously developed with the same goal, i.e. to find the best balance between efficacy and side effects. This is one of the reasons why we chose to proceed with 30 mg dose expansion in our ongoing study, even though we have not yet reached the maximum tolerable dose. By adding an initial dose run-in arm with a lower dose, we further strengthen our program in our ambition to meet the recommendations of Project Optimus. A change that will contribute positively after the completion of the study in our interactions with the FDA and other regulatory authorities.

You’re aiming to kick off the phase IIb study as early as the beginning of 2025. What key milestones must be reached before commencing these studies?

– The first is to establish a collaboration with a CRO and then finalize a study protocol. This then forms the basis for a successful implementation of a so-called study feasibility and application for approval of the study to authorities in the countries where we plan to conduct the study. The work to identify the best CRO partner began at the beginning of 2024 and it is a work that has progressed in a very good way. We have received a great deal of interest from all the companies we have contacted to be involved in this study together with us, so we feel that we have a continued good momentum.

Prolight Diagnostics finalises cartridge design

26 April, 2024

Prolight Diagnostics has completed the design of the cartridge in the Psyros Point-of-Care system. The company’s manufacturing partner FlexMedical Solutions will use the design to develop pilot manufacturing processes, paving the way for clinical validation at the end of 2024.
– This is an important step forward for us in the development process, says COO Karl Bullen.

Prolight Diagnostics is developing Psyros, a portable Point-of-Care (POC) system for measurement of biomarkers at low concentrations. The system has been designed with the intention to support the rule-in and rule-out of myocardial infarction by accurately measuring troponin in blood.

Design finalised for commercial cartridge

The Psyros system consists of a simple and easy-to-use disposable test cartridge and a portable analyser.

Recently, Prolight Diagnostics announced that they have finalised the design of the Psyros cartridge, meaning that the commercial cartridge design has been completed. The company is now focusing on design transfer to its contract manufacturing partner, Flex Medical Solutions. Read more about the partnership here.

Competitive features

The finalised cartridge has several key competitive features, such as a simple design and ease of use. The cartridge is designed with cost-effective components, enabling manufacturing at large scale and low cost of goods.

– The Psyros cartridge has been designed to be very simple. Assembled from only four components, it can easily be produced at large scale using high levels of automation, says Prolight Diagnostics’ COO Karl Bullen in a previous article.

Multiplex-capable technology

The Psyros system is multiplex capable, meaning it can measure multiple biomarkers on a single test cartridge. Moreover, it is compatible with venous blood, fingerstick capillary blood and plasma samples. This ensures the system is versatile and future proofed for new multi-analyte applications.

The commercial cartridge will contain all the reagents required to complete the test, utilizing dried cartridge chemistry. This strategic approach minimises complexity and cost by eliminating the need for expensive liquid reagents/blister packs.

– Throughout the entire design process, each component has been carefully selected for manufacturability, with a strong focus on eliminating the need for complex features and assembly processes. The result of this focused effort is a cartridge design that can be efficiently manufactured from a small number of low-cost components.

COO comments on the development milestone

Biostock talked to Prolight’s COO Karl Bullen to learn more about the cartridge and development milestone.

Firstly, what are your primary responsibilities in the development of the Psyros system?

– As COO I am responsible for daily business operations of Prolight Diagnostics. I am based at the Psyros development site in the UK, where I work closely with the R&D management team to ensure we deliver the Psyros System ready for commercialisation in 2026.

Could you elaborate on the importance of reaching the final cartridge design milestone?

– The finalisation of the cartridge design is a key milestone as it allows our contract manufacturing partner to establish the pilot manufacturing process ready for validation. It represents the culmination of months of development work to ensure the design is both functionally robust and cost-effective to produce.

How do you ensure high quality while managing to maintain low costs?

– Every component has been carefully designed with high volume manufacturing as the focus. Everything from material selection to mechanical tolerances have been carefully modelled and tested extensively at the Psyros development site in the UK to ensure they meet the stringent Quality requirements of ISO 13485 and IVDR. The R&D team have focused on selecting commerically available components, avoided introducing exotic or bespoke materials to keep material costs low.

Could you explain the significance of multiplex-capable technology?

– The ability for clinicians to be provided with measurements of multiple biomarkers from a single sample, quickly and at the point of care will massively improve patient outcomes.

Now that the cartridge design is finalized, what steps will be taken next?

– The Contract Manufacturing partner Flex Medical Solutions is now developing the pilot line, the next step will be testing cartridges from the pilot line with prototype instruments from G&H ITL. Planned for Q3 24, this will allow us to put the system through its paces ahead of the formal validation.

Oncoinvent strengthens board and cash position

24 April, 2024

Oncoinvent has appointed esteemed industry leaders to its Board of Directors, led by Gillies O’Bryan-Tear as Chairman. Furthermore, the company has completed a private placement round of NOK 71 million, which enables advancement to phase IIb with Radspherin. BioStock reached out to Gillies O’Bryan-Tear for a comment.

Oncoinvent is a privately held Norwegian radiopharmaceuticals company, founded in 2010 by Roy Larsen and Øyvind Bruland, who also founded Algeta, Nordic Nanovector and Artbio. Algeta made it to the headlines in 2013 when it was acquired by Bayer for USD 2.9 billion.

Oncoinvent’s lead product candidate is Radspherin, a novel alpha-emitting therapy designed for local treatment of metastatic cancers in body cavities. Radspherin is currently undergoing two clinical phase I/IIa studies targeting peritoneal carcinomatosis from ovarian cancer and colorectal cancer. Interim read-outs are expected in Q4 this year, while final data is anticipated in Q2 2025 for colorectal cancer and Q4 2025 for ovarian cancer.

Capital raise of up to NOK 200 million

Following the IND clearances, Oncoinvent is gearing up to initiate a phase IIb trial with Radspherin in ovarian cancer in Q2. To finance the continued development and manufacturing scale-up, Oncoinvent is currently conducting a capital raise. An initial private placement of NOK 71 million has been completed, mainly directed to internal investors. Oncoinvent aims to secure additional funding from new investors in Q2, up to the limit of the ongoing capital raise set at NOK 200 million.

CEO Anders Månsson estimates that a total capital investment of USD 50 million will be needed to reach the ideal exit point (“ready for phase III”).

Strengthens board for the next phase

To prepare for the next steps in the development, Oncoinvent has appointed new members of the Board of Directors; Gillies O’Bryan-Tear, Ingrid Teigland Akay, Kari Grønås, Hilde Steineger and Orlando Oliveira. Together, they bring a wealth of expertise spanning clinical development, large-scale production, business development and financing.

– The newly elected members of the board will be pivotal as Oncoinvent enters late-stage clinical development, with phase IIb set to commence this quarter. Oncoinvent stands out as the sole independent and privately-owned nuclear medicine company advancing into late-stage development, which puts us in a favourable position towards investors, says Anders Månsson, CEO of Oncoinvent.

Founders will lead Scientific and Clinical Advisory Board

The company’s founding scientist and former board members, Roy Larsen and Øyvind Bruland, will continue to guide the company by leading a newly formed Scientific and Clinical Advisory Board.

– I am very pleased that the founders will continue to contribute to the company by leading the new advisory board. Additionally, we welcome globally recognized experts in radiopharmaceuticals to the Board of Directors. Our leading VC partner Hadean also holds a seat on the board, further strengthening our strategic alignment, says Anders Månsson.

Insights from Gillies O’Bryan-Tear, new Chairman

Oncoinvent’s board will be led by Gillies O’Bryan-Tear, with over 30 years of experience in clinical development, medical management and commercial roles. He has held senior leadership positions at a range of pharma and biotech companies in the US and Europe, including Sanofi Aventis, Bristol-Myers Squibb, GSK, Takeda Pharmaceuticals, and Algeta.

BioStock got in touch with Gillies O’Bryan-Tear to delve deeper into his decision to take on the role as Chairman at Oncoinvent.

First of all, what motivated you to join Oncoinvent as Chairman of the board?

– Well of course the founders Roy Larsen and Oyvind Bruland are old friends from the Algeta days. The technology struck me as typical of their creative approach: an underserved indication (peritoneal cancer) for which there is no really effective treatment; a “simple” idea (all the best ideas seem simple) which should work in the patient population targeted; and the very encouraging early clinical data which speaks for itself. It was an easy decision!

How does your experience and expertise align with the current phase of development at Oncoinvent?

– In the course of my career I have had the privilege to help develop and bring to market a number of oncology medicines, with both large and small companies. I was Chief Medical Officer at Algeta where we brought the first alpha pharmaceutical – Xofigo – to market, and it was the first commercially successful radiation medicine because of its excellent efficacy in prostate cancer. This has led to the founding and growth of a number of radiopharmaceutical companies, including several which have made successful exits recently, such as Rayze-Bio and Fusion (where I was on the Scientific Advisory Board).

– Whilst I was a non-executive director of Clarity, an Australian company developing copper isotopes for a variety of cancers, we listed the company on the ASX in 2021, raising AUD 100 million. I feel that my experience of developing alpha-pharmaceuticals, and on the boards of smaller biotech companies, gives me the right experience to take on the challenge of growing Oncoinvent to the next stage of its own development, and in time bringing Radspherin to market.

What milestones will the initial capital injection of NOK 71 million enable the company to achieve?

– The NOK 71 million, which we hope will rise to 80 million after a repair round, will enable the company to initiate its phase IIb program. As soon as possible, we also want to scale up manufacturing of our lead product, Radspherin, which is essential to supporting a later phase III program.

The company is currently seeking additional funding from external investors. What makes Oncoinvent stand out as a compelling investment opportunity, in your opinion?

– Oncoinvent is the only independently held Radiopharmaceutical company with a product in mid-stage clinical trials. It has in-house manufacturing, and the product targets an area of high unmet need – peritoneal metastases, which are common in ovarian and colorectal cancer. We have data from two phase I/IIa studies which show the product is both well tolerated and has promising evidence of efficacy compared to historical controls. Finally, this is an alpha emitting pharmaceutical, with a high potency and cancer cell kill ratio, and a low risk of bystander toxicity: a favorable therapeutic ratio compared to the much commoner beta emitters.

Curasight gets green light from EMA in phase II prostate cancer trial

22 April, 2024

The partnership deal closed with Curium last year marks the most important milestone for Curasight to date. Now, the European Medicines Agency (EMA) has approved the clinical trial application for the phase II study with uTRACE in prostate cancer.

– The acceptance illustrates the strong progress being made in developing uTRACE, CEO Ulrich Krasilnikoff comments.

Copenhagen-based biotech Curasight focuses on pioneering advancements in cancer theranostics through their proprietary technology targeting the uPAR receptor, a key biomarker for cancer aggressiveness. The company has developed radiopharmaceuticals – the PET-tracer ligand uTRACE and the radioligand therapy uTREAT – serving as non-invasive tools to localise, evaluate and treat multiple types of cancer.

The strategic alliance with Curium, a global leader in radiopharmaceuticals, revolves around the application of uTRACE in diagnosing prostate cancer, potentially offering a less invasive alternative to conventional biopsy methods used in ongoing patient monitoring. Curasight recently received the first milestone payment of a potential total of USD 70 million for the validation of the GMP batch of finished product.

CTA approved

Now, the European Medicines Agency has approved the company´s clinical trial application (CTA), paving the way for a phase II trial with uTRACE in prostate cancer patients.

– The acceptance of the CTA illustrates the strong progress being made in developing uTRACE as a potential solution providing better diagnosis and categorisation of tumours for prostate cancer patients, comments Curasight CEO Ulrich Krasilnikoff.

– It´s also testament to the positive collaboration we have with Curium.

Entering phase II in Q2

The trial is part of the agreed development framework, with Curasight being responsible for the development and Curium heading manufacturing and commercialisation. Preparations are currently underway, with the study aiming at investigating uTRACE as a non-invasive diagnostic tool for the follow up and grading of prostate cancer patients in active surveillance. These patients are often monitored over several years to keep track of the cancer’s aggressiveness.

The study will investigate the Copper-64-labeled version of uTRACE, specifically designed for the US market. One advantage of this version of uTRACE, compared to the Gallium-68-version, is the longer shelf-life, which allows for central distribution from few production sites.

The study design is based on insights gained from previous research and studies conducted with uTRACE, alongside detailed protocol discussions with the US Food and Drug Administration.

– We look forward to dosing the first patient in this phase II trial with uTRACE and to continuing momentum in our efforts to bring uTRACE as a new option for patients, Krasilnikoff says, expecting the first patient to be dosed in the phase II trial in the second quarter of 2024.

Neola’s CEO: “The results from the usability study confirm our product”

22 April, 2024

Neola Medical’s lung monitoring is user-friendly and safe. These are the results of the usability study cunducted during the spring.

– Successful study results are of great importance as we will use them as part of our upcoming FDA application for market approval in the US, says Neola CEO Hanna Sjöström.

Lund-based Neola Medical has developed the medical device Neola, for continuous monitoring of oxygen concentrations in the lungs of premature infants. The medical device enables healthcare professionals to detect and treat complications much earlier than is possible with today’s technology.

During the spring, the company conducted a usability study to see how well healthcare professionals in neonatal intensive care units interact with Neola. The aim has also been to demonstrate that it is safe for its intended use.

Test centre in Boston

The usability study was completed in March, and the collected data has since been evaluated. It was conducted at a test center in Boston in collaboration with Custom Medical, who are global experts in usability studies.

– The study center is designed as a neonatal intensive care unit and the participants in the study consist of 15 neonatal nurses with varying experience from several different neonatal intensive care units in the US, says Neola’s CEO Hanna Sjöström to BioStock.

Positive feedback from the nurses

A number of employees from Neola Medical were on site to train the study participants in the use of Neola. Magnus Johnsson, Director Quality Assurance and Regulatory Affairs, was one of them: Top of the form

– It has been valuable to be on site and see the implementation of the usability study. We have had the opportunity to meet and train the participating neonatal nurses and heard their positive feedback about the potential of Neola.

According to Magnus Johnsson, the nurses found Neola easy to use. In addition, they were able to see the clinical benefit of lung monitoring, which can create good conditions for the product to be well integrated into neonatal intensive care.

Preparing for the FDA application

Neola Medical designed the study after consultation with the US Food and Drug Administration (FDA), in a so-called pre-submission meeting. The final results will be used as part of the company’s upcoming FDA application for market approval in the US.

– Evaluation of usability is a regulatory requirement from the FDA and in order to be approved in the usability study, it is required to be able to demonstrate that the product is safe to use and that risk reduction measures must be deemed effective, concludes Hanna Sjöström.

Medivir’s partner makes clinical progress in veterinary project

19 April, 2024

Medivir’s partner Vetbiolix has reported positive results from a clinical proof-of-concept study in periodontal disease in dogs with one of Medivir’s drug candidates. In a comment to BioStock, Medivir’s CEO Jens Lindberg emphasizes that it is proof of the company’s ability to establish successful partnerships.

In the spring of 2019, Medivir entered into a license agreement for its drug candidate MIV-701 with the French veterinary company Vetbiolix. First-in-human studies with MIV-701, later rebranded as VBX-1000, revealed the candidate to be unsuitable for treating human diseases, but that it has excellent properties for veterinary use.

Upon signing of the agreement, Medivir received a first milestone payment after the product met certain quality requirements. Medivir is entitled to additional milestone payments during its continued development as well as royalties.

Positive results from proof-of-concept study

The candidate has shown potential for the treatment of periodontal disease in dogs, making it the first specific cathepsin-K inhibitor for this indication.

This week, Vetbiolix reported positive results from a clinical proof-of-concept study in periodontal disease in dogs with VBX-1000. The study showed that the medicine was well tolerated, and that the primary endpoint was met. Treatment with VBX-1000 resulted in a statistically significant reduction in CTX1, a plasma biomarker of bone degradation.

Upcoming steps in development

Vetbiolix now intends to conduct a regulatory clinical pilot study to further prove the efficacy of the candidate in a double-blind, randomised, placebo-controlled clinical trial in dogs.

In a press release, Medivir states that the agreement with Vetbiolix only entitles Medivir to minor development and regulatory milestone payments. Rather, the value-creating potential lies in future royalty payments on net sales and/or share of partnering payments that Vetbiolix receives in the event of future partnering agreements with VBX-1000.

Proof of partnering prowess

In the same press release, Medivir states that partnerships and collaborations are central to the company’s business model to accelerate the development of all assets, reduce financial risk and create additional value for shareholders.

Commenting on the positive proof-of-concept results, Medivir’s CEO Jens Lindberg said:

“The positive results with MIV-701 mean that Medivir now has five out-licensed projects, four of which are in clinical phase, creating upside for our shareholders without any additional investments from us. This demonstrates our ability to establish partnerships while confirming the quality of the company’s research and development work.”

Annexin towards completion of phase II study and share issue

18 April, 2024

After reporting promising efficacy signals in the ongoing phase II study on patients with the eye disease RVO, Annexin Pharmaceuticals now has a stronger position in licensing and partnership discussions. To finance continued activities, the company also plans to conduct a rights issue of approximately SEK 45 million, with parts of both the board and management intending to participate. BioStock reached out to CEO Anders Haegerstrand for a comment.

The eye disease retinal venous occlusion (RVO) often results in severe vision impairment or blindness in the affected eye, and today’s standard treatment typically involves monthly drug injections directly into the eye, often over many years. Annexin‘s drug candidate ANXV aims to fundamentally change how these patients are treated by improving vision long-term after just a few days of treatment via a superficial vein in the arm. This can completely or largely reduce the need for today’s type of treatment.

ANXV could also contribute to treating difficult-to-treat cancer forms that currently lack effective treatments.

Progress in Q1

In Annexin’s main project, the ongoing clinical phase II study with ANXV in RVO includes patients who have recently received their diagnosis but have not yet been treated with the standard anti-VEGF therapy.

In February, promising efficacy signals were confirmed in an additional four patients, without any side effects. Six out of eight patients who received 2 mg and 4 mg of ANXV in 2023 showed improved or unchanged visual acuity at the three-month follow-up from treatment, often in combination with reduced retinal swelling and with little or no need for anti-VEGF therapy. In January 2024, treatment of patients with the planned highest dose of 6 mg began. The company aims to present top-line data from the entire study by mid-2024.

Boosting Annexin’s cash position

According to the Q1 report, the company’s liquid assets amounted to SEK 7.9 million as of March 31. To strengthen its cash position, the company plans to conduct a rights issue of approximately SEK 45 million between May 14-28, subject to approval at the annual general meeting on May 2, 2024. The rights issue is 90 per cent guaranteed by existing shareholders, management, and the Board.

CEO’s comments

BioStock contacted Annexin’s CEO Anders Haegerstrand to learn more about the progress in the RVO study and the cancer initiatives, as well as the upcoming capital raise.

Anders, could you tell us more about the progress in the RVO project, especially regarding the efficacy signals you have observed?

– It is very positive that we have not seen any limiting side effects and that six out of eight patients who received ANXV have shown improved or unchanged visual acuity, often in combination with reduced retinal swelling and with little or no need for the standard anti-VEGF treatment. It will be exciting to follow the results regarding patients treated with the highest dose of 6 mg.

You hope to present top-line data in mid-2024. What are your hopes, given a positive outcome, for the continued development?

– If the trend of no troublesome side effects and improvements continues in more treated patients, we will achieve results in line with our high expectations. The strategy is to try to enter into licensing agreements or partnerships for the continued development of ANXV in RVO, but also in other eye diseases.

Your cancer initiative is divided into two projects – an immunotherapy and a conjugate drug. Could you tell us more about your plans?

– The cancer initiative aims to use ANXV both as an immunotherapeutic drug to help the body’s immune system attack cancer cells and as a conjugate drug where ANXV acts as a transporter of chemotherapy directly to the cancer tumor to kill cancer cells. In the first part, we have concrete plans for patient selection we but need to confirm the technique, and once done, we have a good clinical study design for a first patient study. This is an important part of the business development work because partnerships are our main focus also in the cancer area. In the second part, the ANXV conjugate, we await results from studies in animal models in the middle of the year, and thereafter, we believe interest in our cancer initiative will increase.

How do you view the prospects of entering into licensing or partnership agreements for ANXV?

We have always emphasized that the opportunities for a good deal, especially when working with a new disease mechanism, arise only when promising patient data is available, which the RVO study seems poised to deliver. The prospects are good, but the timing is difficult to predict. A conclusion to the RVO study, i.e., when the last patient is fully evaluated, will be important for a good deal. In cancer, we hope that a way to identify suitable patients for ANXV treatment in immuno-oncology, together with more data on the ANXV conjugate, will contribute to making a deal in that area possible as well.

How do you plan to use the proceeds from the upcoming preferential rights issue?

– The majority is planned to be used to complete the clinical phase II study in the eye disease RVO and to conduct preparatory studies in cancer. Additionally, the funds will be used for business development, regular testing, and some product development work on the drug candidate ANXV itself, as well as to maintain and strengthen patent protections.

Medivir continues to accelerate development with fostrox

12 April, 2024

Medivir’s recently published Annual Report for 2023 focuses primarily on the drug candidate fostrox. Clinical data shows improved efficacy in patients with advanced primary liver cancer when the drug is combined with Lenvima. The company continues to accelerate clinical development with the aim of establishing fostrox as the first approved treatment for second-line liver cancer. BioStock reached out to the company’s CEO Jens Lindberg for a comment on the past year, and to learn of his expectations for the rest of 2024.

Patients diagnosed with hepatocellular carcinoma (HCC), the primary form of liver cancer, typically present at an advanced stage of the disease. On the positive side, today’s first-line treatment, Tecentriq/Avastin, has improved the outlook for many patients. On the negative side, many patients stop responding to treatment after some time. For these, there are currently no approved treatments available, i.e. – no alternative in the second line. This is concerning as HCC ranks as the third leading cause of cancer-related fatalities worldwide.

Despite this, many pharmaceutical companies continue to focus on the development of more first-line options. One exception is Huddinge-based Medivir, which has seen the potential for its drug candidate fostrox in the second line, where competition is virtually non-existent.

The goal is to establish fostrox – which has orphan drug designation for the treatment of HCC in the US and Europe – as the first approved option for patients where current first-line treatment is ineffective or not tolerated.

Progress during 2023

The safety and tolerability of fostrox is currently being evaluated in a fully-enrolled phase Ib/IIa study in combination with the cancer drug Lenvima. In March last year, the first patient was dosed in the expansion phase. Thanks to the great interest among investigators and patients to participate in the study, patients were recruited quickly. The last patient was included after the summer.

The initial clinical results indicated a favourable tolerability profile with promising tumour management. Subsequent assessments have revealed, among other findings, a complete tumour response and two partial tumour responses in the first six patients.

During the autumn, the company presented more mature data from the 18 patients in phase Ib/IIa who had undergone at least 12 weeks of follow-up. The results continued to show clear patient benefit with the fostrox + Lenvima combination. The year ended with a positive Type D meeting with the US Food and Drug Administration (FDA) regarding the development plan for fostrox before the first data were presented at the ASCO-GI conference in San Francisco. The data showed further clear signs of clinical benefit and improvement, the longer patients remain on treatment.

Based on these promising data, in combination with the unmet medical need in HCC, the ambition is to conduct a phase IIb study to apply for accelerated approval by the FDA and thus a shorter time to market approval.

The CEO comments

In addition to all the clinical progress achieved in 2023, Medivir also carried out a rights issue in late autumn that provided the company with approximately SEK 129 million, followed by a directed share issue of approximately SEK 20 million when we entered 2024.

BioStock reached out to the company’s CEO Jens Lindberg for a retrospective and an update on the current situation.

Jens, what stands out as the most important factors for the continued development of fostrox?

– A couple of things. On the one hand, there is great interest among investigators and patients to participate in our ongoing study. It is clear that fostrox’s unique, liver-directed mechanism of action is seen as an attractive treatment for advanced liver cancer, which creates the conditions for rapid recruitment in our upcoming phase IIb study. The second is of course the promising data we have been able to show with the combination, and above all that, we see a clearly higher proportion of patients who respond to the treatment and that they benefit from the treatment for longer than can be expected from the treatment options available today.

What conclusions do you draw from the fact that patients continue to benefit the longer they are under treatment?

– The fostrox + Lenvima combination is very well tolerated which is particularly important for patients to be able to remain on and benefit from the treatment for as long as possible. Moreover, it also gives a clear hope for patients, that even if this is advanced liver cancer in the second line of treatment, there is potential for patients to have long-term benefits from the treatment.

You have been successful in raising capital despite challenging economic conditions, particularly within the high-risk life science sector. What do you attribute this success to?

– On the one hand, of course, the data we have shown with Fostrox in liver cancer looks so promising, but I also believe that our positioning of fostrox in second-line treatment, where there are currently no approved treatment options, has also had a positive impact. Of course, I hope that those who have chosen to invest in Medivir also do so because they have confidence in Medivir’s management and employees.

What milestones lie ahead in the coming period?

– Firstly, to confirm the study design of the planned phase IIb study with the regulatory authority in the US and our investigators, while we will also choose a CRO partner to conduct the study.

– Another important aspect is the establishment of partnerships with a focus on Asia for the development and commercialisation of fostrox, where we started the work of finding the right partner(s) at the end of 2023.

– Finally, we are very much looking forward to presenting additional data from the ongoing study at a couple of scientific congresses in 2024, given that such a large proportion of patients continue to be on treatment longer than expected and benefit from the combination.

CLS makes progress in prostate cancer in Europe and the US

12 April, 2024

Clinical Laserthermia Systems has treated its first prostate cancer patients in Italy and secured additional orders and agreements in the US. In addition, the company has presented initial clinical data from the study at Radboud University Medical Center in the Netherlands.

Clinical Laserthermia Systems (CLS) develops and sells TRANBERG Thermal Therapy System, offering focal therapy with laser ablation. Focal therapy selectively eliminates diseased tissue, such as tumours, with high precision and accuracy through high heat generated by laser light. The CLS laser applicator is placed in the target tissue using image guidance.

Need for safer treatment of prostate cancer

The company’s TRANBERG system can be applied in neurosurgery, localized prostate cancer, and oncology. Currently, CLS puts significant emphasis on market expansion within the prostate cancer segment to secure its share of this substantial target market.

Prostate cancer is one of the most common forms of cancer, with over 1.4 million new cases worldwide annually, approximately 350,000 of them within the EU. Today, patients with localized prostate cancer are primarily treated with radiation or radical prostatectomy (surgery), which is associated with significant risks and side effects such as erectile dysfunction and urinary incontinence. Focal laser ablation with the CLS TRANBERG system is a minimally invasive and safer treatment option, with lower risks of side effects.

First patient cases in Italy

Recently, CLS announced that two patients with localized prostate cancer have been treated with the TRANBERG system at San Luigi Gonzaga University Hospital in Turin, Italy. This marks the first time that CLS’s product has been used on Italian patients, a milestone in the company’s commercialisation and expansion in Europe.

The urology department is well renowned and has long experience in targeted prostate biopsies and focal therapy. The clinic performs approximately 450 prostatectomies and more than 50 focal therapy treatments annually. According to CLS, the workflow for the TRANBERG system resembles the process of targeted biopsies, making the implementation of the system a natural next step for the clinic. Dr. De Luca, who performed the treatments, is satisfied with the system:

»”By using our own ultrasound-fusion system for image guidance, we were able to place the TRANBERG Laser Applicators exactly as planned. The integrated tissue temperature control feature of the TRANBERG system was essential to performing precise and safe ablations in these patients. Altogether, we are very pleased with the efficiency and ease of use of this system.«

The experience from the clinic is expected to facilitate the continued expansion in both Italy and other key markets in Europe. CLS’ VP Sales Europe, Perjan Pleunis, emphasizes that Italy is one of the most important markets in Europe, both in terms of market size and knowledge of focal therapy.

Initial data from the Radboud study

CLS has also made progress in the study of prostate cancer. During the European Congress of Radiology, ECR, initial clinical data from the investigator-initiated study at Radboud University Medical Center in the Netherlands were presented. The goal of the study is to investigate the feasibility and safety of the MRI-guided TRANBERG system together with MR thermometry through the CLS Thermoguide for precise ablation control for the treatment of localized prostate cancer.

Principal Investigator Professor Jurgen Fütterer and his team summarised the initial experiences and data from the first six patients in the study. The results indicate a good oncological response and potential improvements in urinary and sexual function. This supports the hypothesis that TRANBERG enables more precise tissue ablation without damaging vital adjacent structures. Read the abstract here.

Second order from National Institutes of Health

In parallel with the development in Europe, CLS is also making progress in the US. The company recently received a second order from the National Institutes of Health (NIH) for accessories for the TRANBERG Thermal Therapy System. The single-use instruments will be used for the ongoing research collaboration with the NIH evaluating the clinical benefit of the TRANBERG products for image-guided (MRI/ultrasound) focal laser ablation for the treatment of prostate cancer.

The goal of the collaboration is to demonstrate that image-guided focal laser ablation is a safe and effective treatment option without the typical side effects often associated with radiation and surgical procedures.

MSP agreement with ROSE Urology

At the end of March, CLS announced that its subsidiary CLS Americas had signed an agreement with ROSE Urology in Florida, USA. The clinic will use the company’s product system for the treatment of patients with prostate cancer, in accordance with the CLS’ Mobile Service Provider model. The model enables clinics to gain quick access to the TRANBERG system and choose from a variety of services according to a fee-per-procedure basis.

The company aims to secure more MSP deals in the US and increase its reach in the prostate cancer segment.

Respiratorius’ US patent application reopens

12 April, 2024

US Patent and Trademark Office's Patent Trial and Appeal Board sides with Respiratorius

After the initial rejection of Respiratorius’ patent application, the US Patent and Trademark Office’s Patent Trial and Appeal Board has now sided with the company. The decision means a reopening of the application regarding the oral formulation of VAL001. BioStock has contacted CEO Johan Drott to gain a better understanding of what this implies for the project.

Lund-based Respiratorius is developing a treatment for diffuse large B-cell lymphoma (DLBCL). The company has developed the drug candidate VAL001 as a pre-treatment to R-CHOP – today’s standard treatment for the disease – that consists of a combination of chemo- and immunotherapy.

In the Q4 report, the company announced having engaged in in-depth discussions with a potential partner for the continued development of VAL001, but that there are still some question marks before an agreement can be reached.

Pursuing two patent applications for VAL001

The company is currently pursuing two patent applications regarding the novel formulation of valproic acid with the patent authorities in intended target markets. The first patent application relates to an oral formulation of valproate and the second concerns the fully developed and more detailed description of the product, where direct release is combined with a sustained release of the active substance.

The patent for the first application was granted in Japan in 2022 and in Canada in 2023. In the US, however, the examiner had objections and chose to reject the company’s patent application.

Successful in their appeal

Respiratorius appealed the examiner’s decision, and the Patent Trial and Appeal Board at the US Patent and Trademark Office (USPTO) has now chosen to rule in favour of the company. The Board annuls all of the examiner’s objections to individual claims. The decision to reject the patent application is overturned, which means that the examiner has to reopen the case.

In connection with the decision, Respiratorius has stated that the Board of Appeal does not see any obstacles to the patent. The company believes that it should therefore be difficult for the reviewer to raise new obstacles to approval. An approved patent would give the candidate protection on the US market until 2036.

The second patent application, relating to the combined release version of the candidate, was filed in the summer of 2023. This process has not come as far, but if the company receives the green light for this patent, it means that the protection of VAL001 will be extended for another 20 years.

Comments from the CEO

BioStock reached out to Johan Drott, CEO of Respiratorius, to get his view on the US Patent Office’s decision.

Johan, can you elaborate on what the USPTO’s latest ruling means for the protection of VAL001?

– A patent approval in the US naturally strengthens the case. Our US Patent Attorney is monitoring the progress of the proceedings at the US Patent Office closely. To be clear, this does not mean that the patent has been approved in the US, but it means that the application is reopened.

You believe that it should be difficult to raise new obstacles to the patent. When do you a final decision?

– Right now, I cannot comment on when a possible approval of when the patent application may be approved. This depends on how the reviewer decides to act. Our US counsel has attempted to reach the reviewer for a meeting.

You are running another patent application process in parallel, relating to the latest formulation. Does the USPTO’s new decision have any bearing on that application as well?

– The latter application has not yet reached the international stage and is completely independent of the decision of the Patent Trial and Appeal Board.

You are currently conducting an in-depth partnering dialogue. How is that affected by the US Patent Office’s decision?

– We have not specifically discussed patent applications in this dialogue. The painfully long discussion relates to other issues, more specifically the design and implementation of a phase III study. Such a large investment is a major decision-making commitment.

12 3...147 Page 1 of 147