Aptahem, whose primary drug candidate Apta-1 is being developed as an acute treatment for sepsis, recently announced that it is expanding its team with Suzanne Kilany as Clinical Research Director. The recruitment comes as the company prepares to move into clinical development with its main candidate. Kilany, who most recently comes from a position as Medical Scientific Adviser (MSA) at Astellas Pharma, is also a long-time board member of the Swedish Pharmaceutical Society’s clinical studies department. Here, she tells BioStock more about her new role at Aptahem.
SuzanneKilany has been hired as a consultant by Aptahem for the role as Clinical Research Director (CRD). Her job is to lead and coordinate the planning and preparation for the company’s upcoming phase I clinical trial with their drug candidate Apta-1. With its drug candidate, Aptahem wants to improve the treatment outcome in sepsis, a disease that kills 11 million people globally every year.
»Being able to sit on the board of the Swedish Pharmaceutical Society’s department for clinical studies means that I have a network of colleagues that I can turn to and it is also a very good way of keeping up to date on what is happening and what the requirements are« — Suzanne Kilany, CRD Aptahem
Suzanne Kilany, CRD, Aptahem
BioStock contacted Suzanne Kilany to find out more about why she chose to take on the challenge of leading the clinical development work at Aptahem, and what hopes she has for the candidate Apta-1.
Suzanne, congratulations on your new position! What made you accept this role?
– Most large companies conduct their early drug development outside Sweden, which means that I have mainly worked with the later development phases. Getting involved from the beginning in the development of a new drug candidate is incredibly exciting, and when I was offered the opportunity and the privilege of this assignment at Aptahem, it was not difficult to accept.
You have three decades of experience with clinical studies and clinical development work, including at pharma giant Astellas Pharma. What specific lessons do you take with you from your previous positions that may be useful in your new role as CRD at Aptahem?
– The most important lesson is that communication is absolutely crucial. Furthermore, that the work is a team effort regardless of which side of the table you are on and that everyone should feel involved in both the work and the results. There are many factors involved in the process; for example, several different government approvals are required for clinical development. It is also necessary to build networks and relationships with medical specialists and to build trust in Aptahem. It is a process that takes a lot of time. Thorough preparatory work is extremely important in order to achieve a good end result.
»The preclinical results show that Apta-1 is an interesting drug candidate even in other therapy areas such as osteoarthritis, viral infections and various types of cancer«
During your career, you have had extensive contacts with both pharmaceutical companies and contract research organisations, and, at the same time, you are a board member of the Swedish Pharmaceutical Society’s department for clinical studies. In what way will this benefit you in your future work?
– I bring with me the way of thinking from both clients and from contract companies. Above all, I have knowledge of the regulations and know that you have to be pragmatic in order to move forward with a maintained quality. Being able to sit on the board of the Swedish Pharmaceutical Society’s department for clinical studies means that I have a network of colleagues that I can turn to and it is also a very good way of keeping up to date on what is happening and what the requirements are.
What, in your opinion, makes Apta-1 interesting?
– Apta-1 is an aptamer-based drug candidate, and today there is only one registered aptamer product on the global market. There is a huge medical need for the intended treatment area and treatment indication for Apta-1. The preclinical results show that Apta-1 is an interesting drug candidate even in other therapy areas such as osteoarthritis, viral infections and various types of cancer.
Phase I clinical trials with Apta-1 are getting closer, and your primary task will be to lead and coordinate planning and preparation work ahead of this milestone. What will this mean in more concrete terms?
– I will of course work with the clinical development plan and, among other things, look at the best location for carrying out the phase I clinical trial and find the right CRO with the skills, qualifications and experience of conducting studies in critical conditions. The challenge is to find a measurable endpoint that is established and accepted by medical expertise, such as survival.
What milestones do you see ahead and how do you plan to ensure that these are reached?
– The basis for initiating clinic studies is largely already available, such as preclinical and toxicological studies. What remains in order to be able to proceed to clinical studies is the GLP-toxicology study. In the meantime, we are preparing the study design, taking in quotes and discussing with potential clinical investigators. As this is based on teamwork, everyone should be aware of the milestones and be constantly updated. It requires being proactive and one step ahead.
»The goal is to attract a licensing partner after completing phase I/II in order to continue the development. An alternative scenario is to find a partner before entering clinical studies, based on a precise development plan«
Apta-1 is being developed as an acute treatment for sepsis. How large do you think the need for a new drug within this indication is and do you think the public has a fair idea of how deadly the disease is?
– Sepsis is a serious condition, which affects approximately 49 million people annually and kills 11 million each year. For Sweden, the corresponding figures from 2016 are 40,000 affected and about 8,000 (20 per cent) dead each year. The public is generally unaware of how deadly this condition is, or what it is. The number of patients diagnosed with sepsis hides a significant number of unrecorded cases as many underlying diseases can cause the condition, such as cancer, influenza infections and many more. There is a great need for a new drug for sepsis as it does not always have to be a deadly outcome, but the condition can have other lasting and, sometimes lifelong, consequences.
Finally, in terms of your new position, what awaits you in the near future?
– My focus right now is to first familiarise myself with the results that already exist and get to know the team. What I will address first is to create a development plan for Apta-1 that extends to clinical phase II and plan and prepare for phase I (First in Human, FiH). The goal is to attract a licensing partner after completing phase I/II in order to continue the development. An alternative scenario is to find a partner before entering clinical studies, based on a precise development plan.
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.
The Lund-based inhaler experts Iconovo are on the front lines of the fight against asthma, and they recently announced a new partnership dedicated to the development of ICOres budesonide/formoterol, the generic for AstraZeneca’s Symbicort, which is currently on the market for the treatment of asthma. BioStock was able to talk with Iconovo’s CEO Johan Wäborg to discuss the implications of the partnership and what it means for the ongoing battle against asthma.
Yesterday, May 5, 2020, was World Asthma Day, a day dedicated to raising awareness about the respiratory illness affecting millions around the world. In short, asthma is a chronic inflammatory airway disease that represents a global health problem with an increasing prevalence in many countries, especially among children, and it imposes a high burden on society.
Although some countries have seen a decline in hospitalizations and deaths from asthma, the illness still imposes an unacceptable burden on healthcare systems associated with costs related to hospital services, doctor visits, and medicines. The societal burden is also quite heavy through loss of productivity in the workplace from both patients and caregivers and through disruption to families feeling the strain of a loved one suffering from the disease.
Asthma affects 235 million people
According to the World Health Organization (WHO), asthma is the most common chronic disease among children, and it is estimated that around 3-4 per cent of the global population is affected by the disease. A Global Asthma Networkreport from 2018 outlined that globally, asthma is ranked 16th among the leading causes of years lived with disability and 28th among the leading causes of burden of disease, as measured by disability adjusted life years (DALYs). Regarding the economic burden of asthma, it varies from country to country, however, for the EU it reaches about 20 BEUR annually, according to a study from 2012.
Asthma medication can be given in the form of a tablet as well as intravenously, but metered-dose inhalers (MDIs) and dry powder inhalers are the most common drug delivery systems in the case of asthma. With these, the medicine is delivered directly to the lungs, resulting in faster symptom relief. Moreover, this type of drug delivery has shown to cause fewer side effects overall.
Iconovo in the fight against asthma
Swedish medtech company Iconovo is at the forefront of developing dry powder inhalers for the treatment of several respiratory illnesses, including asthma. The company also develops generic formulations to go along with the inhalers that correspond to some of the main products already on the market. One of the company’s four inhaler platforms is ICOres.
Since 2016, Iconovo has developed a generic form of AstraZeneca’s Symbicort Turbuhaler (budesonide/formoterol), which is currently on the market for the treatment of asthma as well as COPD. The original product is valued at 2.5 BUSD annually. Iconovo’s project involves using the company´s multi-dose reservoir inhaler, ICOres, as the delivery system for a generic formulation of the asthma drug.
Iconovo partners with Amneal Ireland Limited
Late last week, Iconovo announced that the Symbicort generic project would be transferred to Amneal through the Irish subsidiary, Amneal Ireland Limited, from the CBC Corporation. Amneal’s Co-Chief Executive Officer Chintu Patel had this to say about the recent developments in the press release:
Developing a range of inhalation products remains an important element of Amneal’s portfolio strategy. Amneal expects that combining Iconovo’s extensive experience in inhalation development with Amneal’s capability to bring complex generic medicines to market will set this partnership apart.
Iconovo’s newly appointed CEO, Johan Wäborg, expressed his enthusiasm towards the new partnership:
Iconovo welcomes Amneal as a development partner for our Symbicort project. As we are closing into making larger investments in the project, we feel that Amneal is best positioned to support the project with the required resources and give certainty to the development track. It is a key priority for Iconovo to reach the patients in a timely manner to benefit from the turnover related royalty payments to the company. We look forward to working with Amneal on this exciting project.
BioStock was able to catch up with Iconovo’s CEO to get his perspective on the importance of this partnership, the implications regarding the generic Symbicort project moving forward, and what it all means for asthma patients in the long run.
Johan Wäborg, CEO at Iconovo, could you go into more detail about the terms of the partnership with Amneal?
– The terms are unchanged and the original partner obligations remains the same. For us, it is important to reach the market with certainty and in a timely manner. An important component of the terms is that Iconovo is entitled to royalties on the net sales and that should be a significant future revenue generator.
Why is the partnership with Amneal important to Iconovo?
– Amneal is dynamic company with a willingness to invest to keep timelines. Getting to market with ICOres budesonide/formoterol is a key priority to Iconovo as it is a significant business opportunity.
In the press release, you mention closing in on making new investments in the Symbicort generic project. How much can you divulge about such investments?
– There are still significant investments to be made by our partner in pharmacokinetic clinical trials and manufacturing set-up to get to market. Exactly how large of an investment to be made is a matter for our partner to decide. Amneal are ready to make the needed investments.
Johan Wäborg, CEO at Iconovo
Yesterday was World Asthma Day. What implications do you expect Iconovo’s Symbicort generic project to have for asthma patients in the long run?
– ICOres budesonide/formoterol will be the first generic Symbicort product that truly has the same operation as Turbuhaler. It will make it easier for the patients to switch to ICOres to find a more affordable medicine. In addition, they will get some valued feedback features like an exact dose counter and a visual indicator that they have inhaled correctly. On top of that, I hope you agree that the design is appealing and importantly, it also feels good to hold and use.
Finally, what milestones do you see for the project in the near future?
– The next milestone will be the upcoming pharmacokinetic (PK) study as the first PK study showed that the product needed some adjustment to fully match the reference product, although coming in very close to bio-equivalency.
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.
Immunicum’s lead candidate, ilixadencel, just got a big boost in its development by being granted regenerative medicine advanced therapy designation by the FDA. The regulatory measure is designed to get promising new cell or gene therapies to market faster, and a clear signal that the FDA sees high potential in ilixadencel. BioStock reached out to Immunicum’s COO Sijme Zeilemaker to learn more about the news and what it means for ilixadencel moving forward.
Developing a new, innovative drug for the treatment of a serious disease and getting it to market involves several steps, which can take years, if not decades. Some of the steps are regulatory requirements necessary for providing evidence that a compound is safe for humans and, of course, effective in treating the indicated disease. However, with biomedical technology changing at a faster and faster pace, the bureaucracy aimed at keeping patients safe is, in some cases, preventing promising medicine from reaching the patients on time.
Read more about the challenges in drug development in BioStock’s 5-part article series on drug development here.
Speeding up the drug development process
In recent years, major regulatory bodies like the Food and Drug Administration (FDA)in the US or the European Medicines Agency (EMA) in the EU have tried to answer the call for speeding up the drug development process. This is particularly the case for cell and gene therapy biological drugs, which rely on technology that is quickly evolving.
Over the last decade, the FDA has put in place regulatory directives aimed at helping companies get their products to the market more quickly, especially for drugs meant for treating a serious medical condition and that fulfils an unmet medical need. These directives include Fast Track and Breakthrough Therapy, among others. While Fast Track is mainly aimed at expediting the review process for FDA approval, Breakthrough Therapy includes all the benefits of Fast Track plus intensive guidance from FDA officials through all stages of clinical trials.
Regenerative Medicine Advanced Therapy designation
Most recently, in 2017, the FDA implemented a directive called Regenerative Medicine Advanced Therapy (RMAT). The aim of this designation is similar to Breakthrough Therapy, but with a focus on regenerative medicines like cell or gene therapies, which have a more dynamic regulatory environment in general compared to biologics or small molecules due to the fast pace of evolving technology behind them.
RMAT gives companies several benefits. One of the most important benefits is the eligibility for increased and earlier interactions with FDA officials to expedite development and review of the therapy. Overall, the designation gives companies more confidence in their development programs, knowing that their candidates meet the high standards put in place by the FDA. It also helps smoothen the path to market by greatly strengthening the chances of approval.
Immunicum granted RMAT
This week, one of Sweden’s top immuno-oncology (IO) companies, Immunicum, just received notice of being granted RMAT from the FDA for its main candidate, ilixadencel, for the treatment of renal cell cancer (RCC) patients. The FDA’s decision was made based on the results from the MERECA trial presented at the ASCO-SITC conference earlier this year.
Initial analysis of the ongoing Phase II exploratory clinical trial that evaluated the safety and efficacy shows an improved response in patients given ilixadencel in combination with a tyrosine kinase inhibitor (TKI) called Sutent (sunitinib), which is commonly used for treating some cancers. Read more.
Exciting times at Immunicum
This is exciting news for the Swedish biotech as the RATM designation is sure to have a positive impact on the company’s development program by helping to further establish the next steps for the MERECA trial. The excitement was shared by Immunicum’s CEO Alex Karlsson-Parra:
We are very excited to have received the RMAT designation for ilixadencel in kidney cancer as it recognizes both the potential of our novel therapeutic approach as well as the clear need for viable therapies to address this difficult-to treat disease. As a designation similar to the FDA’s Breakthrough Therapy Designation, we will now also have the opportunity to receive direct guidance from the FDA which will inform key development decisions and ultimately bring us closer to delivering ilixadencel to patients in need.
BioStock talked with Immunicum’s COO Sijme Zeilemaker about the FDA’s decision.
Sijme Zeilemaker, this is a big step forward for Immunicum and ilixadencel’s development program in particular. What was your reaction to this news?
– Honestly, I jumped up from my desk. The RMAT designation has been something we have been eyeing, yet with only a few dozen breakthrough therapies being granted this relatively new instrument from the FDA, you have to contain yourself to avoid getting your hopes up. We have been increasingly enthusiastic about the clinical observations from the Phase II MERECA study the more we looked into the results and as data further matured, but having the regulatory authority confirm this from an independent perspective is truly exciting.
We have already mentioned some of the benefits of the RMAT designation, but could you point out what you believe to be the most important benefit(s) for ilixadencel’s development?
– The two-way dialogue allows Immunicum to work together with the FDA in finding the best path forward. Cell therapy is a transformative modality; however, this also means that both the company and the regulatory authority are learning along the way. Instead of asking closed questions and hoping for positive regulatory responses after completing the development program, this ensures that each development step we undertake to the market has been vetted by the FDA. This should substantially improve our development success rate and time to market.
Sijme Zeilemaker, COO at Immunicum
How will this decision by the FDA impact the timeline for the MERECA trial?
– Our next development steps in kidney cancer will be further informed by the feedback from the authorities (both FDA and EMA), and the next survival update from the MERECA study mid 2020. Now, we will have the opportunity to have more regular meetings from Q3 onwards, after the already planned meeting with the FDA end of Q2 2020. These steps are crucial for establishing the path in RCC and pursuing partnering and other options of moving this program forward.
Finally, will this decision by the FDA have any impact on other development programs in Immunicum’s pipeline? If so, to what extent?
– Being granted this RMAT designation for kidney cancer, it also paves the way and supports a strategy of establishing similar proof-of-concepts as with the MERECA study in other indications, for which, subsequently, such RMAT designations can be requested to accelerate the path to the market. This is highly aligned with Immunicum’s aim to position ilixadencel as a safe and effective immunotherapy add-on to treatment of various solid tumours with a high unmet need.
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.
Saniona, currently redeeming the first out of three outstanding warrants, is approaching late-stage clinical studies with lead candidate Tesomet in two eating disorder indications. Meanwhile, partner company Medix is getting ready to launch its licensed asset tesofensine as a new obesity drug following a successful phase III study in Mexico. BioStock had a talk with Saniona’s US based CEO Rami Levin, who after 23 years in the industry will use his experience to attract major US biotech investors to the company.
Rami Levin was named new CEO of the Danish biotech company Saniona in January. Living and working out of Boston Massachusetts, USA, he has been active in the pharmaceutical industry for over 23 years with a strong focus on rare diseases and CNS. His most recent role was as president of Sobi Inc., the US subsidiary of the Swedish biopharmaceutical specialist company which is dedicated to rare diseases.
At Sobi, Rami Levin was responsible for building the US organization and leading it through a successful growth period. He also led the launch of Gamifant, the first ever approved treatment for primary hemophagocytic lymphohistiocytosis (pHLH) and the integration of the team behind Synagis, the only approved treatment for respiratory syncytial virus (RSV).
Prior to his time at Sobi, he held leading commercial positions at Merck Serono in a number of countries, including the US, Switzerland, Israel and Sweden – thus, Rami Levin is certainly no stranger to the Nordic biotech ecosystem.
BioStock reached out to Levin to get his view on the company´s path to market with lead compound Tesomet and the key activities he has planned, going forward.
Rami Levin, CEO, Saniona
Rami Levin, what are the three most important focus areas for Saniona at the moment?
– The most important focus area right now for Saniona is to ensure we have the financing required to be able to focus on the three main company goals:
To advance the clinical development of Tesomet in both rare eating disorders: Prader Willi Syndrome and hypothalamic obesity all the way to registration and commercialization.
To advance the earlier stage molecules: SAN711 and SAN903 into phase 1 clinical trials and beyond
Build a full-fledged presence in the US, the largest rare disease market in the world.
On April 22nd the company announced positive topline results from the phase II trial with Tesomet in Hypothalamic Obesity (HO). The data concluded that Tesomet is safe and well-tolerated in HO patients and that the treatment led to statistically significant reductions in the key efficacy endpoints, weight loss, waist circumference and glycemic control compared to placebo. Could you elaborate on the importance of these findings, moving forward?
– Patient’s suffering from HO typically do not respond well to lifestyle modification techniques such as diet or exercise and there are currently no drugs approved for this patient population. Although several drugs are used off-label, they maintain limited efficacy because they have not been specifically developed for this patient population.
– Our findings support the continued development of Tesomet for patients with HO, highlighting that the treatment is safe and well tolerated and provides significant relief for the core symptoms associated with this disorder. The response from the patient community and treating physicians has been very positive. We look forward to communicating our findings to the FDA as we work towards initiating future studies.
You are also evaluating Tesomet as a potential therapy for Prader-Willi syndrome (PWS). Last year, Saniona reported positive phase IIa clinical results in patients with PWS with data providing guidance for the pivotal Phase IIb/III studies. How far along are you in planning the upcoming pivotal phase III study in this indication?
– Saniona is planning to meet with the FDA in Q2 for a pre-IND meeting. In preparation for this meeting Saniona has worked diligently in planning and preparing the robust phase IIb study design, which we intend to discuss with the FDA.
– Following the meeting with the FDA we intend to submit an IND for approval, which is necessary in order to be able to conduct clinical trials in the US. Once approved we will kick off our planned phase IIb trial, which we hope can start before the end of the year.
»Tesomet provides its effect via an established mechanism of action that is relevant to both syndromic and nonsyndromic forms of obesity, providing an avenue to potentially developing the compound across multiple obesity disorders« — Rami Levin, CEO Saniona
The active substance tesofensine has evolved from initially targeting just obesity, to – in the form of Tesomet – being well on its way to the market in both HO and PWS, two serious eating disorders that currently lack treatment options. What is the nature of the competitive landscape in these indications and what would you say differentiates the mechanism of action in tesofensine/Tesomet from its competitors?
– As a result of the amazing patient advocacy work that has been performed in PWS over the past decade, there has been a growing number of companies showing an interest in this disorder. Just this year there have been three Phase III clinical trials of various compounds in PWS. Although not all will be successful (one actually failed just recently), we are encouraged by this interest as it supports the high unmet need in this patient population and the urgency for developing multiple treatment options.
– Hypothalamic obesity is less well known than PWS, but growing support from patient organizations is increasing public awareness and generating interest from industry. Saniona is the only company that we are aware of that is actively pursuing the development of a novel treatment for HO and we are excited to continue our progression towards market approval. Tesomet provides its effect via an established mechanism of action that is relevant to both syndromic and nonsyndromic forms of obesity, providing an avenue to potentially developing the compound across multiple obesity disorders.
The roadmap ahead includes a so-called End of phase-meeting with FDA regarding upcoming trials in both HO and PWS. Can you tell us more about what these meetings usually entail?
– The end of phase meetings are intended to review the results of the trials with the FDA and receive advice and guidance from them on future clinical development plans for the product.
– In Saniona’s case these meetings will also serve as pre-IND meetings. An IND approval from the FDA is required to be able to conduct clinical trials in the US. As none of the Tesomet trials so far been conducted in the US an IND was not required. However, moving forward all of our clinical trials will be conducted in the US, and therefore will require an IND. These meetings therefore will help shape the IND submission to the FDA.
»We are specifically grateful for the trailblazing work that the Raymond A. Wood Foundation is doing in advocating for hypothalamic and pituitary brain tumor survivors, many of whom develop HO«
Following your positive data from the HO study, you have had a lot of interest from patient organizations in the US who are of course hopeful and eager to see a potential new therapy on the market as soon as possible. How important is it to get the support from these organizations, before entering the market?
– It is critically important for any company working in the rare disease space to be engaged with patient organizations. These organizations are a voice for the patients and we always strive to listen to this voice to ensure studies are designed to address patient needs. Rare disease drug development requires input from multiple stakeholders, and we see the patient organizations as being paramount to our success.
– We are committed to building awareness for HO and to improving the understanding of the mechanism of disease in the hope that new treatment options can be made available. We are specifically grateful for the trailblazing work that the Raymond A. Wood Foundation is doing in advocating for hypothalamic and pituitary brain tumor survivors, many of whom develop HO.
»In some cases we need to define key and meaningful endpoints in our clinical trials, be creative in recruiting patients into those trials or develop and define metrics to measure success, which never existed before«
From a regulatory and a commercial perspective, since there are currently no viable therapeutic drug alternatives out there for HO or PWS patients, what “success level” in terms of clinical data is required to make a powerful entry on the market?
– Being a company focused on rare diseases, where usually no other treatments are available on the market often means that we need to trailblaze our way to product approval. This means that in some cases we need to define key and meaningful endpoints in our clinical trials, be creative in recruiting patients into those trials or develop and define metrics to measure success, which never existed before.
– Saniona is committed to the highest quality science. In our pursuit to bring novel treatments to the market for patients with the highest unmet needs, we will be working closely with the input from the patient organizations and the FDA to guide us.
Saniona has a broad candidate portfolio in addition to the eating disorder projects. Some of your projects are already partnered and even close to commercialization, and some are earlier stage assets which you aim to develop internally. Could you very briefly guide us through the pipeline, and give a short comment on the commercial strategy for each asset?
– Our proprietary rare disease pipeline is our main value driver. Tesomet is our most advanced treatment in development and is now approaching late stage registration studies in both PWS and HO. Saniona intends to continue developing Tesomet up to registration and then commercialize it ourselves.
– Saniona also has two earlier stage proprietary programs: SAN711 and SAN903. Both molecules represent very innovative and potentially game changing new treatment principles in severe, rare itching disorders and inflammatory disorders, respectively. Here as well, we intend to develop both of these molecules and ultimately commercialize them ourselves.
– Apart from our proprietary products we also have strategic partnerships and out licensing agreements on some of the molecules we discovered for larger indications. The most advanced treatment, which is closest to approval is tesofensine for treatment of obesity. We have out licensed tesofensine to Medix in Mexico and Argentina. Tesofensine is now in registration phase in Mexico with expected approval and launch later this year. Once approved and launched, Saniona will start to receive royalties on sales.
Just over a month ago, the ongoing collaboration that Saniona has with Boehringer Ingelheim resulted in a second research deal, what can you tell us about that?
– We have been working successfully with Boehringer Ingelheim for several years focusing on schizophrenia. Boehringer Ingelheim has taken one of Saniona’s ion channel programs covering GABAa5 into preclinical development. The new research collaboration between Saniona and Boehringer Ingelheim covers an entirely new and innovative ion channel target with a strong link to schizophrenia. The new drug class is intended to treat negative and cognitive symptoms of schizophrenia, which are often the most critical obstacles for patients to engage in social life.
For a company with a broad pipeline, especially in late clinical stage, financing the ongoing development is usually a high stakes game. In January, Saniona completed a private placement of SEK 25 million and proposed a financing solution which could provide up to SEK 158 million. It is actually a combination of the directed issue, a loan of SEK 25 million and a rights issue of three series of warrants at a strike price of SEK 25–30 per share. Can you tell us more about this financing model and how far it will get you, provided that the warrants are executed?
– We are entering an exciting phase for the company, with both an expansion of our presence in the important US market, as well as meaningful progress on our drug development programs. The net proceeds from the financing solution you describe will enable Saniona to focus our efforts on three main areas:
Further advance the development of our key asset Tesomet for the two eating disorders: Prader-Willi syndrome and Hypothalamic Obesity. It will allow us to initiate the phase IIb/III clinical trial in Prader-Willi syndrome before the end of the year and the phase IIb/III clinical trial in hypothalamic obesity in Q1 2021.
Advance our earlier pipeline products including SAN711 and SAN903 into phase 1 clinical trials and beyond.
As we are now also entering a new phase for the company, transforming Saniona into a global, fully integrated biopharmaceutical, with a strong presence in the US, the largest rare disease market in the world.
»There is no treatment available for either Prader Willi syndrome or hypothalamic obesity, so bringing Tesomet to the market and making it available to these patients who desperately need it is critically important to us«
In conclusion, if we take a quick look into the crystal ball, where would you like to see Saniona in 12 months from now?
– In 12 months from now I would like to see Saniona as a well-funded company, allowing us to focus our efforts on advancing on all three main company goals. There is no treatment available for either Prader Willi syndrome or hypothalamic obesity, so bringing Tesomet to the market and making it available to these patients who desperately need it is critically important to us.
Watch BioStock’s latest video interview with Rami Levin
”The real growth will come from our proprietary projects” (May 5, 2020)
Click here for more information on the exercise of warrants of series TO 1.
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.
The peptide specialist company Follicum has filed an international patent application for its topical cream formulation. The application is both relevant for the company’s furthest-advanced candidate, FOL-005, which is currently undergoing a clinical phase IIa study in hair loss, but also includes the formulation as carrier for other peptide drugs intended for topical application on the skin. An approved patent would open the door to new opportunities for Follicum.
Follicum develop peptide-based drugs with a focus on hair growth and diabetes. The company’s primary candidate is FOL-005, developed to stimulate hair growth in hair loss (alopecia) patients, is currently undergoing a phase IIa clinical trial in Germany.
Previous clinical studies with the candidate applied the FOL-005 substance using intradermal injections. But with the end consumer in mind, Follicum has developed a topical formulation of the candidate, i.e .a cream that can administers the drug by topical application on the scalp. The purpose of the more practical formulation is to promote its user-friendliness and the commercial prospects of the final product.
It is this topical formulation of FOL-005 that is now being tested in the ongoing phase IIa study.
See CEO Jan Alenfall give the latest status update regarding the Phase IIa study in a video interview with BioStock here [in Swedish].
Developing a topical formulation is complex
Formulating peptides so that they remain stable for a long time in a topical formulation is a very challenging task. Furthermore, getting the peptide to be transported into the skin, and, as in the case of FOL-005, to the hair follicle, requires extensive development work. The company has therefore worked closely with reputable experts in formulation development and has thus been able to evaluate various formulation technologies in a methodical way – and it gave results.
The new topical formulation of FOL-005 has been shown to efficiently release the active substance into the skin and hair follicles. It has also been found to have a good safety profile. In addition, the topical formulation is stable in long-term storage, which is crucial for the product to be used for long-term treatments. From a commercial perspecitve, it is also very important to ensure optimal manufacturing and storage, facilitating a cost-effective logistic process. In addition, Follicum has expressed that the formulation can be considered cosmetically attractive, which is important for the treatment to be initiated, and completed, by the end consumer –the patients.
Jan Alenfall, CEO, Follicum
Read more about the substantial consequences of hair loss and why an effective treatment is needed here.
Applied for an widened patent
To this background, Follicum has filed an international patent application (PCT) regarding the company’s topical cream formulation as a carrier of peptide substances. The application includes new experimental data that support the potential use of the formulation for several peptide drug substances. An approved patent would extend the protection of FOL-005 by at least 8 years, but it would also mean that the company obtains a patent for the use of their cream formulation as a carrier of other peptide drugs administered topically on the skin – for indications other than alopecia. This would broaden the potential for Follicum’s topical formulation technology.
Follicum’s CEO Jan Alenfall commented on the patent application:
»We are very pleased to have developed a robust formulation of FOL-005 that the patient can use in a simple way. The challenges in developing functional, topical formulations of peptides, are to ensure that breakdown of the peptides is prevented, and to optimize their properties so that the product penetrates the skin. We have managed to meet these challenges with the new formulation, which has a long shelf life and is simple and very attractive for the patient to use. Based on this progress, we have filed an international patent application covering the use of the formulation for other peptides«
Creates new opportunities
The company is yet to comment on whether they plan to expand its pipeline with additional topical peptide based drugs, or if the patent primarily constitutes a base for outlicensing such assets to external players. At this point in time, both paths are equally likely, and should be expected a bit further down the line.
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.
NeuroVive Pharmaceutical has long recognised the importance of working closely with leading researchers. Since 2016, the Lund-based company that develops drugs primarily for mitochondrial diseases, has partnered with the American Children’s Hospital of Philadelphia and the University of Pennsylvania to further develop its projects. Two recent scientific articles linked to these collaborations now show how NeuroVive’s succinate prodrugs can have broad positive effects in mitochondrial medicine. BioStock got the chance to talk to some of the researchers behind these publications.
NeuroVive Pharmaceutical has over twenty years of experience in its primary focus area of primary mitochondrial disease. The mitochondria exist inside our cells to create the energy needed for us to properly function. For an individual affected by a primary mitochondrial disease, energy production in the mitochondria does not function as it normally would, which can lead to cell damage and unnecessary strain on the body’s organs to perform their basic functions. Overall, this can affect bodily functions such as growing, moving and breathing.
American collaborations
Among the institutions that NeuroVive works with are the Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania (PENN). CHOP is not only one of the world’s largest paediatric hospitals and ranked as one of the very best hospitals for children in the United States, but it also houses the renowned Mitochondrial Disease Clinical Center, a centre for children and adults suffering from mitochondrial diseases.
Focus on succinate prodrugs
NeuroVive’s partnerships with CHOP and PENN focus primarily on mitochondrial diseases and how the company’s NVP015 program can be used to develop treatments against these. The NVP015 project is based on a concept developed by Eskil Elmér, NeuroVive’s CSO and an adjunct professor at Lund University, in close collaboration with chemists at British company Isomerase Therapeutics. The concept is based on the body’s own energy substrate succinic acid – succinate – being made available inside the cell via so-called prodrug technology. A prodrug is an inactive drug substance that is activated only when it enters the body when its chemical structure changes.
The most common cause of primary mitochondrial disease is genetic defects that affect the first of five enzyme complexes found in the mitochondrial respiratory chain involved in mitochondrial energy production: complex I. NeuroVive’s succinate prodrugs directly target the stimulation of complex II and bypass the defective complex I. Thus, with a succinate prodrug, the energy substrate, which itself cannot normally penetrate the cell wall, can be inserted into cells in organs that need to be supported due to mitochondrial disease. Mitochondrial damage can also occur as a result of, for example, poisoning and other external effects.
Repeated injections of soft money
NeuroVive’s partnership with CHOP has attracted significant financial grants from heavyweight US organisations. In 2018, one of these collaborative projects was awarded a three-year grant of 4,090,281 USD by the US Department of Defense’s Office of the Congressional Directed Medical Research Program. The aim of the project was to study the effects of NVP015 substances in experimental models of primary mitochondrial diseases.
The NVP015 project was led by Dr Todd Kilbaugh, Associate Professor of Anaesthesiology, Intensive Care and Paediatrics, who is also responsible for a project that was awarded a 473,000USD grant from the National Institutes of Health (NIH) in 2017. The grant was received to study NVP015’s ability to support mitochondrial function recovery and prevention of organ failure after direct exposure to toxic chemicals.
At home, the NVP015 / NV354 project has been awarded two research grants from Vinnova totalling 6 million SEK.
On its way to clinical studies
One of the most important steps to date in the NVP015 project was the selection of the candidate substance NV354 for continued development in primary mitochondrial diseases. NV354 is now in preclinical development, and, following good results there, NeuroVive expects to complete the documentation required in 2020 to be able to initiate clinical studies during the first half of 2021. The candidate targets Leigh syndrome, the most common congenital mitochondrial disease among children. The affected children have very severe symptoms and often die before the age of five.
Noted project has resulted in licensing agreements
But it is not only researchers, hospitals and authorities that have been interested in NeuroVive and the company’s candidates. The NVP015 program has also paid off in the form of an out-licensing agreement with a total potential value of 60 million USD. In 2018, molecules from NVP015 were licensed to BridgeBioPharma. BridgeBio founded a subsidiary, Fortify Therapeutics, which develops the molecules for targeted treatment of Leber’s hereditary optic neuropathy (LHON), another example of a primary mitochondrial disease.
An agreement with a leading distributor
The factor mainly responsible for the great interest in NeuroVive’s NVP015 substances is the fact that they are cell-permeable, which means that they possess the ability to enter cells and affect complex II in the mitochondrial respiratory chain. Succinate prodrugs stimulate complex II. NeuroVive, in collaboration with Isomerase, has also produced a cell-permeable prodrug of the endogenous substance malonate, which in turn inhibits complex II. This gives researchers in mitochondrial physiology and medicine more tools to evaluate cell and mitochondrial physiology as well as the role of mitochondria in diseases, in cellular models.
MitoKit-CII
Last year, NeuroVive signed an exclusive commercial agreement with Oroboros Instruments. The Austrian company is a world leader in the development and distribution of analytical instruments and reagents for research and development in mitochondrial medicine. Today, Oroboros Instruments includes two of NeuroVive’s prodrugs – NV118 (succinate prodrug) and NV161 (malonate prodrug) – to all customers who purchase their equipment, which means a significant distribution of NeuroVive’s prodrugs sold under the name MitoKit-CII. The fact that such a heavy player like Oroboros Instruments chooses NeuroVive’s prodrugs must be seen as an important recognition of the company’s research on mitochondrial medicine.
Generates scientific articles
The company’s prodrugs are used commercially as well as through NeuroVive’s extensive collaboration with various research institutions. The latter has now led to two new, interesting scientific publications. In early April, a study was published using NeuroVive’s prodrug NV241. The purpose of the study was to investigate mitochondria as a potential therapeutic target in the treatment of paracetamol overdose, which is common and can lead to severe liver damage. The study, conducted in cellular models, showed that NeuroVive’s succinate prodrug could ’rescue’ mitochondrial respiration after acute paracetamol poisoning. BioStock has spoken with lead author Sarah Piel, PhD, researcher at CHOP, about the study and NeuroVive’s prodrugs.
Sarah Piel
Firstly, Dr Piel, this study is not the first time you have worked with NeuroVive. Can you tell us a bit more about your connection to NeuroVive?
– In my PhD in Mitochondrial Medicine from Lund University I evaluated cell-permeable succinate prodrugs, one of NeuroVive’s pharmaceutical strategies (NV015), as potential treatment for drug-induced mitochondrial dysfunction. The cell-permeable succinate prodrugs were originally developed as therapeutic for genetic mitochondrial disease, with mitochondrial complex I being most commonly affected.
– Because succinate is used for energy production by mitochondrial complex II it can bypass complex I and serve as an alternative energy substrate. Like in genetic mitochondrial disorders, mitochondrial complex I is also a common target for a wide range of drugs and highly metabolic tissues are often a target of drug-related toxicities. Therefore, acute intoxication due to intentional or accidental overdose presents an additional target indication which can benefit from this pharmaceutical concept.
Can you briefly describe the purpose of the current study?
– In this study we evaluated the mitochondrial toxicity of the common pain killer paracetamol (acetaminophen) and how cell-permeable succinate prodrugs can counteract that dysfunction. Paracetamol is the most common over-the-counter pain medication used worldwide. Although generally considered safe at therapeutic dosage it is the most common cause for acute liver failure in the western world.
– Currently, the only one clinically approved treatment option for paracetamol overdose is the antioxidant N-acetylcysteine which primarily protects healthy liver cells from paracetamol rather than rescuing the already damaged cells. Therefore, alternative treatment options are needed targeting the latter cell population. Mitochondrial dysfunction plays a critical role in the development of paracetamol-induced liver injury and therefore we wanted to investigate whether cell-permeable succinate prodrugs have potential as treatment strategy to counteract paracetamol-induced liver injury.
Can you elaborate on how NeuroVive’s prodrugs were used and what results you achieved?
– In this study we used NV241, one of the main candidates of the first generation of cell-permeable succinate prodrugs, generated before NV354 was developed. These earlier compounds are ideal for lab studies whereas NV354 has been optimised for clinical use.
– We simulated acute intoxication of human derived liver cells with paracetamol and evaluated treatment efficacy following paracetamol overdose ex vivo while continuously monitoring oxygen consumption to assess mitochondrial function. Following acute exposure to paracetamol mitochondrial complex I-linked but not mitochondrial complex II-linked oxygen consumption was impaired. We then showed that treatment with the cell-permeable succinate prodrug NV241 rescued paracetamol-induced impaired mitochondrial respiration.
What, according to you, does the results say about the potential of NeuroVive’s prodrugs within the treatment of paracetamol overdoses?
– The results of our in vitro study present pharmacological bypass of paracetamol-induced mitochondrial toxicity with cell-permeable succinate prodrugs as a promising alternative treatment strategy for paracetamol-induced liver injury.
– The next step in developing cell-permeable succinate prodrugs as treatment for paracetamol-induced liver injury is to evaluate their treatment efficacy in vivo in experimental models of acute paracetamol overdose to bring it closer to clinical application.
Are there any other treatment areas where you can see potential for NeuroVive’s prodrugs?
– Here at the Children’s Hospital of Philadelphia and under the lead of Todd Kilbaugh, Associate Professor of Anesthesiology, Critical Care, and Pediatrics, we have developed a pre-clinical drug development platform to evaluate mitochondrial-targeted therapeutics. With the aim to find effective treatments for acute critical illnesses where mitochondrial function is negatively altered this drug-development platform will be used to lead novel, mitochondrial targeted therapeutics through the pre-clinical drug development stage. NeuroVive’s prodrugs are the first therapy that is evaluated using this platform.
– The cell-permeable succinate prodrugs are investigated as treatment to counteract energetic deficits and prevent multi-organ failure following acute exposure to chemical warfare agents, toxic industrial agents and pesticides. This work is funded by the NIH program CounterACT. Like in acute drug overdose, mitochondrial complex I is a common target of many chemicals and there is scientific evidence that chemically-induced mitochondrial dysfunction contributes to long-term morbidity and mortality following acute chemical exposure.
– Improving mitochondrial function with the cell-permeable succinate prodrugs is a novel approach for drug development in this area which recently lead to a publication entitled “Mitochondrial respiratory chain complex I dysfunction induced by N-methyl carbamate ex vivo can be alleviated with a cell-permeable succinate prodrug” in the journal Toxicology in Vitro. In this study, we demonstrated that cell-permeable succinate prodrugs can rescue bioenergetic deficits induced by n-methyl carbamates, a chemical class of commonly used insecticides.
– Currently, NeuroVive’s prodrugs are further evaluated in our pre-clinical drug development platform in cellular and other experimental models of acute chemical poisoning with the organofluorine Sodium Fluoroacetate, the organophosphate Diisopropylfluorophosphate, and, under the lead of Dr David Jang, University of Pennsylvania, carbon monoxide and cyanide. Because the cell-permeable succinate prodrugs do not act on the chemical agent itself but act as a countermeasure to compensate for toxic injuries I believe it is widely applicable as pharmacological strategy for chemical poisoning and drug overdose related critical illnesses.
Recently, another study using one of NeuroVive’s prodrugs was published. In this case, a research group at PENN investigated how to use NV118 to improve mitochondrial function in cells from patients with carbon monoxide poisoning. BioStock has spoken with lead author David H. Jang, assistant professor, University of Pennsylvania Perelman School of Medicine, Department of Emergency Medicine and Division of Medical Toxicology.
To begin with, what was the aim of this study?
David H. Jang
– The paper that was recently accepted for publication in the American Journal of Physiology-Cell Physiology is entitled, “Ex vivo use ofcell-permeable succinate prodrug attenuates mitochondrial dysfunction in blood cells obtained from carbon monoxide poisoned individuals.”
– The aim of this study was to examine mitochondrial dysfunction in carbon monoxide (CO) poisoning using blood cells as a surrogate marker from patients with acute CO poisoning. We have performed two prior studies that show that blood cells may be a better marker of clinical severity of disease then a carboxyhemoglobin (CoHB) and that the standard treatment for CO, which is hyperbaric oxygen may have adverse effects such as increased generation of radicals.
How was NeuroVive’s NV118 used in this particular project?
– In this study we applied the use of NV118 (ex vivo) in the same blood cells obtained from acutely CO poisoned patients. We were able to demonstrate a rescue effect of partial Complex IV inhibition of CO and overall improved mitochondrial respiration with the use of NV118.
– Also important to our work is the Oroboros O2k. One of the issues with in vitro cyanide and carbon monoxide work is the potential for off gassing so this may effect results. The self-contained chambers of the O2k ensures that the work we do with the succinate prodrug is accurate and reproducible.
If we look at the bigger picture, can you tell us about how you use NeuroVive’s prodrugs in your research?
– First, I would also like to acknowledge our multidisciplinary team at the University of Pennsylvania and the Children’s Hospital of Philadelphia along with Lund University. The research I am pursuing is only made possible with my collaboration with Drs. Sarah Piel, Johannes Ehinger and Todd Kilbaugh who I know are quite experienced in the field of mitochondrial medicine and critical illnesses, especially in regard to the succinate prodrug.
– With that being said as a Medical Toxicologist, my research has been focused on investigating therapeutics in Complex IV poisoning. The common one medical toxicologist provides care for are agents that include CO, cyanide, hydrogen sulfide and phosphides. Taken together these are all very potent poisons with high mortality and morbidity with exposure. Unfortunately, there are no good reliable treatments for these agents which rely on supportive care and antidotes that have variable treatment effects. As it is well known, the field of mitochondrial-based therapeutics is limited, and the succinate prodrug have a lot of potential to change treatment in the field of toxicology
What characteristics do NeuroVive’s prodrugs possess that make them useful for your research?
– One of the big questions that remains in the treatment of Complex IV poisoning is what the effect of increasing Complex II respiration with the succinate prodrug will have on Complex IV inhibition. As a toxicologist, in many cases of Complex IV inhibition, there will be functional CIV activity and that the use of the succinate prodrug may be helpful in this instance.
– We also recently submitted a manuscript describing the use of the succinate prodrug in an in vitro model of cyanide poisoning where we were able to demonstrate increased respiration with partial Complex IV inhibition with cyanide and attenuation of radical production (superoxide). Having a potential treatment that could be administrated in the field with efficacy is critical in my field that these succinate prodrugs provide.
Finally, what are your future plans regarding research with NeuroVive’s prodrugs?
– Our group’s future plan is focused on the in vivo application of the succinate prodrug in experimental models of poisoning. We anticipate the funding of an NIH award to evaluate this succinate prodrug in an experimental model of CO poisoning. Drs. Piel, Ehinger and Kilbaugh as well as myself plan to also evaluate the succinate prodrug in another, more advanced, experimental model with also potential NIH funding. Our group is poised for effective preclinical trials with the expectation for clinical application in the near future and an opportunity to offer treatment to people with severe intoxications.
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.
Cereno Scientific develops innovative medicines for cardiovascular and rare diseases related to fibrosis, thrombosis, inflammation and high blood pressure in the lung as well as systemically. As a step towards a more international footprint, the Gothenburg based company has established a US subsidiary in Boston called Cereno Scientific Inc. This is in line with the company’s ambition to scale up collaborations and networks with business partners and potential investors across the Atlantic Ocean.Just over a year ago, in March 2019, Cereno Scientific announced the formation of a Scientific Advisory Board (SAB) intended to support the company’s scientific and clinical development. Dr Bertram Pitt, Professor of Medicine Emeritus at the University of Michigan School of Medicine in Ann Arbor, USA and a highly regarded cardiology expert, was named chairman of the SAB. In addition, two of five SAB members are Boston based; Dr Deepak Bhatt and Dr Gordon H Williams, both affiliated with Harvard Medical School.Read more about the SAB members below.
Expanded scope and added assets
The formation of the SAB was the first step towards expanding Cereno Scientific’s portfolio, which, at that point, consisted of the main candidate CS1 being developed as a preventive antithrombotic drug. During the spring of 2019, that was about to change.
The SAB swiftly identified a wider indication potential for CS1, starting with larger cardiovascular indications related to fibrosis and inflammation such as atrial fibrillation, heart failure and chronic kidney disease within the field of epigenetic modulation based on the histone deacetylase (HDAC) inhibitory effect of the active substance in CS1, valproic acid (VPA). It was further identified that CS1 had a potential arterial pressure lowering effect in the lung, and rare diseases such as Pulmonary Arterial Hypertension (PAH) and Chronic Thrombo Embolic Pulmonary Hypertension (CTEPH) became of interest.
Today, Cereno Scientific’s drug development pipeline focuses on preventive treatment of thrombosis and rare fibrosis-related vascular lung diseases. It consists of CS1 aimed for thrombosis prevention and PAH/CTEPH where the PAH project received an Orphan Drug Designation (ODD) from the FDA in March. To further advance this opportunity, world leading PAH specialist Dr. Raymond L. Benza was recently recruited as a Scientific Advisor. Read more.
Moreover, Cereno Scientific’s portfolio also includes a preclinical HDAC inhibitor program.
Sten R. Sörensen, CEO, Cereno Scientific
US subsidiary to promote business opportunities
Alongside the broadened scope of the CS1 asset and the ODD status granted by the FDA, Cereno Scientific started to look for additional opportunities in the US. With an ambition to advance the company’s US network, both in terms of current and future collaborative business partners as well as potential investors, establishing a US subsidiary seemed like a natural step forward.
CEO Sten R. Sörensen, with extensive experience from innovative drug development in the cardiovascular space, commented on the news:
»The establishment of our subsidiary Cereno Scientific Inc. in the United States is strategically important for the growth of Cereno. The United States is the world’s largest financial market and Kendall Square in Cambridge, Boston, is considered to be one of the leading biotech cluster in the world. We are excited to increase our proximity to important potential collaborators and investors and to join many other important biotech companies in Cambridge.«
Cereno Scientific Inc. at CIC
As referenced by Sörensen, the established subsidiary, Cereno Scientific Inc., has its office at the Cambridge Innovation Center (CIC) at Kendall Square in Cambridge, Boston, in proximity of SAB members Dr Bhatt and Dr Williams as well as a vibrant community of leading edge universities, biotechs and investors specialized in the life science sector.
CIC itself is known for being a cluster of innovative life science companies and is thus a natural habitat for an up-and-coming company like Cereno Scientific. BioStock is looking forward to learn more of how the company will capitalize on this exuberant and stimulating environment.
Members of Cereno Scientific’s SAB
Dr Bertram Pitt (chairman), Professor of Medicine Emeritus at the University of Michigan School of Medicine in Ann Arbor, USA and a highly regarded cardiology expert.
Dr Deepak Bhatt, Professor of Medicine at Harvard Medical School, a well-renowned expert on thrombosis and currently Executive Director at Brigham and Women’s Hospital.
Dr Gordon H Williams, Professor of Medicine at Harvard Medical School since 1981 and heading a research group focusing on the genetic aspects of diseases within cardiovascular, endocrinology, diabetes, and metabolism.
Dr Faiez Zannad, Professor of Cardiology at Université de Lorraine and head of the department for heart failure, hypertension and preventative cardiology at Centre Hospitalier Universitaire de Nancy in Laxou, France.
Dr Gunnar Olsson, MD and PhD with great experience from several leading positions within pharmaceutical R&D, e.g. more than 20 years at management level in AstraZeneca generating extensive experience of both product development and life cycle management for pharmaceuticals.
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.
The field of immuno-oncology encompasses several strategies to push our own immune system to be more sensitive and reactive to cancer cells and metastases. Swedish biotech Immunicum have developed their own strategy and were asked to present and discuss it on a panel of immuno-oncology experts at the 31st Annual Cancer Progress Conference last week. BioStock caught up with Immunicum’s COO, Sijme Zeilemaker, who represented the company on that panel, to learn more about the discussion and how Immunicum is making a difference in the field.
Immuno-oncology (IO) has made a name for itself in the realm of cancer therapy as one of the most promising solutions to this deadly disease. The field has generated several treatments based on the use of immune cells, e.g., adjuvant immunotherapy, T-cell therapies, and checkpoint inhibitors (CPIs), over the past decade and has been able to bring down the mortality rate for most cancers. However, the need for even better treatments remains high, and several immuno-oncology strategies are currently being devised as potential solutions.
Different IO approaches to fool cancer
One of the main reasons cancer is so deadly is the fact that cancer cells are able to evade the defence mechanisms of the immune system in order to keep multiplying within the body. Therapies based on IO have become popular thanks to their ability to teach the immune system to be more receptive to cancer cells and thus become more reactive before the cancer takes over the body.
However, IO is a complex field that involves testing several innovative approaches for priming the immune system to better fight cancer. No one yet knows which strategy or combination of strategies will deliver the best treatments, but the topic is often a major point of discussion at international conferences focused on oncology.
One of these approaches is to develop an off-the-shelf allogeneic cell therapy able to be injected inside the tumour itself and cause a chain reaction within the immune system where inflammatory molecules called chemokines and cytokines call upon killer T-cells to recognise and attack the tumour cells.
Immunicum pitches off-the-shelf IO approach at state-of-the-art conference
The off-the-shelf allogeneic cell therapy approach is the one taken by Stockholm-based Immunicum, who have been testing their top candidate, ilixadencel, in Phase II clinical trials with Metastatic Renal Cell Carcinoma patients (the MERECA study). To find out more about their approach and the Phase II study, read here.
The company was invited to present at the 31st Annual Cancer Progress Conference, which was held virtually due to the Covid-19 pandemic between May 5 and 6, 2020. The conference itself was organised by Cello Health, and brought together innovators in the field from all over the world. It also featured the participation of major oncology institutions like the Cancer Research Institute, a non-profit organisation dedicated to advancing immunotherapy for treating and curing cancer, which refers to immunotherapy as “the most promising treatment of our time.”
COO of Immunicum Sijme Zeilemaker participated at the conference by taking part in a panel discussion titled, Paradigm-shifting platforms I, IO: Taking IO to the next Level. He was joined by representatives of six other companies working on different IO platforms, and they all pitched their innovative initiatives using their respective strategies. See the full program and list of panellists here.
BioStock reached out to Sijme Zeilemaker to ask him about the discussion and how Immunicum’s IO strategy fits within the field.
Sijme Zeilemaker, COO at Immunicum
Sijme Zeilemaker, first of all, what does it mean to you and to Immunicum as a whole to be able to participate in a panel discussion at this cancer conference?
– It is great to be recognised as a novel platform among all the exciting developments in the highly competitive field of immuno-oncology. The unique character of our approach was central to being part of this panel of paradigm-shifting platforms, in which highly differentiated platforms that may become the future of cancer therapy shared the spotlight.
Could you summarise, in a few words, the take-home message of the panel discussion?
– Science is moving at an extraordinary pace especially in the field of IO in which the high unmet needs create this urgency of development. The overlapping message from these different platforms was that the future of cancer therapy requires a highly personalised and tumour-specific immune response induced by a more potent and broader mechanism of action. This mechanism of action should involve different classes of immune cells, preferably combined with an off-the-shelf manufacturing ability to be able to address patients across the globe in a cost-effective way. The advent of cell therapies and allogeneic platforms was crucial to this discussion.
Immunicum’s main candidate, ilixadencel, is a so-called off-the-shelf allogeneic approach. In simple terms, what does that mean exactly?
– It means that this cell therapy does not derive from the patient’s own cells, but can be produced from a healthy donor (thus allogeneic), and thereby in a more consistent, cost-effective and scalable manner. Specific to our mechanism of action, our cells are able to be derived from healthy donors as we activate these specific immune cells to become inflammatory dendritic cells (DCs) as the central kick-starters of immunity against the tumour. The allogeneic nature of the cells actually contributes to this mechanism, activating the patient’s own immune cells as the ones to ultimately carry out a strong and sustained tumour-specific immune response.
»Ultimately, the hope of immuno-oncology is not just to delay cancer growth as with more traditional cancer therapies, but to lead to durable tumour decreases and even potential cures. Immunicum has observed this where the treatment of ilixadencel induced more durable and complete responses in its recently completed Phase II study in kidney cancer« — Sijme Zeilemaker, COO at Immunicum
How does this approach differ from some of the others presented at the panel discussion?
– The panel included approaches to enhanced tumour radiation, an allogeneic mixed cell therapy, and bispecific antibodies. Each is able to address parts of the cancer immunity cycle, i.e. all elements of the immune system needed to recognize and attack cancer, by for example inducing immunogenic tumour cell death, activating Natural Killer (NK) cells, or stimulating the expansion of immune cells.
– Unfortunately, cancer has established itself with multiple defence mechanisms, and only targeting one such mechanism while leaving open other pathways allows for cancer evasion and escape. Immunicum’s ilixadencel primarily addresses this by focusing on a more complete mechanism of priming the immune system: by injecting inflammatory DCs in the immunosuppressive environment of the tumour and inducing a cascade of immune cells, such as NK cells, bystander DCs and killer T cells, to counteract the tumour cells.
In broader terms, how does Immunicum’s approach stack up with other IO approaches being used, in terms of benefit for the patient, and why do you think the Cancer Research Institute refers to immunotherapy as “the most promising treatment of our time?”
– Our preclinical and clinical data suggest that this more complete mechanism of action is synergistic to systemic therapies such as kinase inhibitors and checkpoint inhibitors to enable the activated immune response to fully carry out its cancer-killing ability. Ultimately, the hope of immuno-oncology is not just to delay cancer growth as with more traditional cancer therapies, but to lead to durable tumour decreases and even potential cures. Immunicum has observed this where the treatment of ilixadencel induced more durable and complete responses in its recently completed Phase II study in kidney 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.
During 2020, Clinical Laserthermia Systems has received market approval in Europe for its MR-led minimally invasive soft tissue treatment product, the TRANBERG Thermal Therapy System, as well as for its new Thermoguide thermometry software, for of which are used for treatment in organs such as the prostate and the brain. At the end of last week, the company also issued an update regarding the corresponding application for approval in the US. BioStock has talked to CEO Lars-Erik Eriksson about what this means and what next step is for CLS.
Lund-based Clinical Laserthermia Systems (CLS) works with image-guided laser ablation treatment of soft tissue, such as cancer tumours. In short, laser ablation means that laser light is led into the tumour, which causes the temperature of the cancer cells to rise and them to be destroyed. The treatment procedure is guided by ultrasound or magnetic resonance imaging (MRI). Thermoguide, CLS’s new thermometry software, is adapted for MRI and allows the physician, with high precision, to control the temperature and see the treated area of the tumour throughout the procedure.
CLS’s products can be used for both focal laser ablation (FLA / LITT), as well as for the company’s proprietary immune-stimulating interstitial thermotherapy (imILT) method, which not only kills the tumour but also has the potential to affect the immune system so that any metastases shrink or are completely eliminated.
Approval in Europe
So far this year, CLS has taken several steps forward with both the TRANBERG Thermal Therapy System and Thermoguide. In April this year, the company received EU approval for Thermoguide as well as a renewed EC certificate for the TRANBERG Thermal Therapy System, including the associated software. This means that CLS’s products can now be sold in Europe for use in treatment indications such as prostate cancer, brain tumours and epilepsy.
Evaluation in Germany
More good news regarding the TRANBERG Thermal Therapy System came in March when CLS announced that the University Hospital in Magdeburg, Germany is evaluating the system for the treatment of small liver metastases. So far, the treatment has worked well and no side effects have been noted in the patients. At the end of April, the university hospital placed another order for disposable materials within the framework of the collaboration, which means that CLS has now invoiced the hospital a total of 220,000 SEK.
Read more about the collaboration with the University Hospital in Magdeburg here and here.
Further preclinical studies required for FDA approval
While working on the European approval, CLS has also filed an application to the FDA to obtain the corresponding approval for the TRANBERG Thermal Therapy System including Thermoguide for the US market. With regards to the TRANBERG Thermal Therapy System, the product already has FDA approval. The company has had a continuous dialogue with the FDA, during which it emerged that the FDA has more extensive requirements for preclinical studies than expected, especially for products to be used in the neuro-field.
So, at the end of last week, CLS announced that it will launch preclinical in vivo studies in both neuro and prostate treatment. The studies will start during the current quarter, and the company expects the studies to continue during the rest of 2020.
BioStock had the opportunity to ask a few questions of CLS’s CEO Lars-Erik Eriksson about the FDA application.
Lars-Erik, the FDA has decided that preclinical in vivo studies are needed for your application. Can you tell us a bit more about why the FDA makes this assessment?
Lars-Erik Eriksson, CEO at CLS
– Laser ablation is an established treatment alternative for the treatment of, among other indications, brain tumours and epilepsy. In recent years, the FDA has tightened the requirements for ablation products for use in the brain. The reason for this is that there were systems on the market that did not work well enough, even though they formally met the FDA’s requirements. Now the requirements have been tightened and since the TRANBERG system has not been used in this area before, it is natural for the FDA to be meticulous. The brain structures are very sensitive and therefore we must show that the product meets all the requirements and behaves in the same way as equivalent products in the area. It is about patient safety and that is just as important to us as it is to the FDA.
More specifically, what is it that the in vivo studies will examine?
– In the in vivo studies, treatment of brain and prostate tumours is performed in living tissue. This means that you can follow up on the treatment and ensure that no side effects occur after the end of treatment, which is of course essential. The FDA has also requested that the tissue destruction, which Thermoguide continuously calculates during a treatment, be correlated with other established methods, e.g. MRI contrast measurements and tissue histology. These types of evaluations will also be included in the preclinical study.
You expect to start the studies during this quarter, which of course places high demands on CLS’s internal organisation and resources. Do you have all the parameters in place to be able to start this venture so quickly?
– On the one hand, it places demands on our internal organisation but also on the external parties that will carry out parts of the work. We have hired a research institute in the US that meets current FDA requirements for preclinical studies, and we have a close collaboration with ClearPoint Neuro, who will conduct the studies with us.
When do you expect to be able to submit a complete application to the FDA?
– According to the plan, we should be ready to submit an application during the first half of 2021, when all analyses and compilations of the pre-clinical studies are ready.
You have FDA approval for the TRANBERG Thermal Therapy System, and a number of hospitals in the US are already using the system. How, if at all, does this delay in approval for Thermoguide affect your work with marketing and sales of the TRANBERG Thermal Therapy System in the US?
– We will market the system in the US for prostate treatment, just as we are doing today, and we can also present Thermoguide and talk about the work that is being done to obtain approval for the product. We will continue to market and sell our disposable patient care instruments as we are currently doing now. However, we cannot sell the system integrated with Thermoguide in the US as we can Europe. Given how the coronavirus pandemic seems to be evolving, we see great opportunities to work with our hospital contacts in Germany, France and Iberia where we have already established contacts. In the US, we have sales resources locally through our own staff and through ClearPoint Neuro. We will be as effective as we can based on the conditions provided.
CLS products offer laser treatment with high precision
The CLS TRANBERG Thermal Therapy System includes a laser unit specially developed to be user-friendly, a system for monitoring and controlling tissue temperature as well as sterile disposable products that are replaced for each treatment session. The system measures and displays the temperature at various points in the tumour tissue and can be used in conjunction with all available image control techniques.
In addition, CLS has also developed a new software, Thermoguide, which, in combination with CLS laser systems, provides doctors with information on both temperature development and tissue destruction in real time. The fact that ablation can be monitored in real time enables the treatment to be optimised for each individual patient.
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.
Iconovo’s strong start to 2020 shows no signs of slowing down as we approach summer. The company just added a CE marking to the list of reached milestones, making the company’s capsule-based dry powder inhaler ICOcap authorized for use in clinical trials by European customers. BioStock takes a closer look.
Lund-based medtech company Iconovo has shown a good measure of resilience during the coronavirus pandemic. Not only have the inhaler experts been marginally impacted economically (read more here), but they have also managed to stay on track with their planned activities after carrying out a directed share issue raising 60 MSEK at the end of 2019.
A lot going on in 2020 so far
All the while, Iconovo has reached several important milestones with its inhalation platforms. In March alone, the company announced two Intentions To Grant by the European Patent Office (EPO), one for ICOres, and one for ICOone – two of Iconovo’s four inhalation platforms. A further intention to grant notice for ICOres came from the EPO a month later.
What is more, a new partnership with Amneal Ireland Ltd was announced earlier this month. The project is dedicated to the development of ICOres budesonide/formoterol, the generic for AstraZeneca’s Symbicort. Like Symbicort, Iconovo’s reservoir-based multi-dose inhaler ICOres and a dry powder formulation are used to treat asthma and COPD, and the global market value for the drug combination product is estimated at approximately 2.5 billion USD annually. Read more.
Internal changes
In the midst of an active first part of the year, Iconovo also underwent some changes internally. The company took steps to improve investor relations by restructuring its website, making it more detailed and easier to navigate.
At the same time, Iconovo added international strategic business development experience to its management team by appointing Johan Wäborg as CEO, while OrestLastow, the company’s previous CEO, has taken the CTO position to focus on developing new inhalation platforms for Iconovo.
CE marking for ICOcap
Now, with summer on the doorstep, Iconovo can add another major milestone to its repertoire for 2020. Yesterday, the company announced that its capsule-based dry powder inhaler ICOcap had received a Class I Medical Device certification in conformity with the requirements of Directive 93/42/EEC. This CE marking means that European customers who produce dry powder formulations for treating asthma and/or COPD can now purchase ICOcap from Iconovo’s manufacturing and distribution partner, Stevanato Group, and use the device in clinical trials.
Iconovo’s newly-appointed CEO talks about how important this is, not only for Iconovo, but also at an international level:
Getting the CE certification mark for ICOcap takes Iconovo and Stevanato one step closer to commercial sales of this uniquely designed capsule inhaler. The inhaler can now be sold for use in clinical trials. This is not only of importance for Europe but also for the rest of the world since the CE marking globally is considered as a sign of quality.
ICOcap is available in two versions and has the same function and performance as the established capsule-based dry powder inhaler HandiHaler from Boehringer Ingelheim, or dry powder inhaler Breezhaler from Novartis. Iconovo’s device has a unique design that makes it robust but also easy to use, as well as making it able to handle different capsule sizes. Furthermore, the inhaler can be optimized according to customer needs in order to provide maximum product performance for a given drug formulation.
High expectations for the months to come
A recent analysis by Danske Bank describes how Iconovo represents a significant market opportunity as its current product portfolio addresses a market worth 14 BUSD in annual product sales. Read more. The analysis expects Iconovo to continue gaining momentum in the market thanks to its strong business model, and the high growth in sales.
As the company continues to reach important milestones, BioStock is looking forward to following Iconovo going forward.
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.
– I bring with me the way of thinking from both clients and from contract companies. Above all, I have knowledge of the regulations and know that you have to be pragmatic in order to move forward with a maintained quality. Being able to sit on the board of the Swedish Pharmaceutical Society’s department for clinical studies means that I have a network of colleagues that I can turn to and it is also a very good way of keeping up to date on what is happening and what the requirements are.
– My focus right now is to first familiarise myself with the results that already exist and get to know the team. What I will address first is to create a development plan for Apta-1 that extends to clinical phase II and plan and prepare for phase I (First in Human, FiH). The goal is to attract a licensing partner after completing phase I/II in order to continue the development. An alternative scenario is to find a partner before entering clinical studies, based on a precise development plan.
Although some countries have seen a decline in hospitalizations and deaths from asthma, the illness still imposes an unacceptable burden on healthcare systems associated with costs related to hospital services, doctor visits, and medicines. The societal burden is also quite heavy through loss of productivity in the workplace from both patients and caregivers and through disruption to families feeling the strain of a loved one suffering from the disease.
The company also develops generic formulations to go along with the inhalers that correspond to some of the main products already on the market. One of the company’s four inhaler platforms is ICOres.
This week, one of Sweden’s top immuno-oncology (IO) companies, 
– Our findings support the continued development of Tesomet for patients with HO, highlighting that the treatment is safe and well tolerated and provides significant relief for the core symptoms associated with this disorder. The response from the patient community and treating physicians has been very positive. We look forward to communicating our findings to the FDA as we work towards initiating future studies.
well as a renewed EC certificate for the TRANBERG Thermal Therapy System, including the associated software. This means that CLS’s products can now be sold in Europe for use in treatment indications such as prostate cancer, brain tumours and epilepsy.
