Hello, and welcome back to DNB Carnegie. We are continuing our Microcap Healthcare Day. Next up we have Ascelia Pharma, and I have Magnus Corfitzen with me, CEO of Ascelia Pharma. Welcome.
Yeah. Thank you.
I'll briefly update you on the format. We will start with a presentation where you talk about what you do, where you stand, and what the future may hold for Ascelia. After that, we will continue with a Q&A session. I remind everyone to please ask questions in the chat. I'll be on the lookout, and hopefully we'll get a lot of answers today.
Yeah. Absolutely.
Please take it away.
Thank you, Maria. It's great to be here and present Ascelia Pharma. I will be making a number of forward-looking statements. At Ascelia Pharma, we identify, develop, and commercialize novel drugs addressing unmet medical needs for people with rare cancer conditions. We're based in Malmö, Sweden, and traded on Nasdaq Main Market. We have a pipeline of two products. The lead program, which I will spend most of my presentation discussing today, is Orviglance, a first-in-class diagnostic drug for liver MRI in patients with severe renal disease. We have FDA Orphan Drug Designation, and we submitted the new drug application, the NDA, on September 3 last year. In mid-November, we received a Day 74 letter from the FDA recognizing and accepting the submission for full review.
They have set a PDUFA date, which is when they expect to have a decision on approvability, on July 3 this year, so less than four months away. We also have Oncoral. I'll spend a few minutes talking about that at the end. It's a very exciting program, but still early in development. First, I'll talk about Orviglance. Let me start by highlighting why we are so excited about it. We've been working on this asset for years, and now we are very close to the timeline for approval. First of all, which I think is essential in any drug development, Orviglance addresses a well-defined unmet medical need in patients who require liver imaging and who have severe renal problems. They have challenges with the existing options available today.
We solve that with Orviglance. That translates into an $800 million addressable market opportunity globally. We have manufacturing in the U.S., and the manufacturing capacity is sufficient for global supply, so we are able to scale up and support any needs that patients have. The documentation for the program is supported by nine different clinical studies. These studies show consistent results, especially the Phase 3 pivotal study with strong enhancement of the liver. As mentioned, the NDA has been submitted to the FDA, and they are currently reviewing it. We are also preparing a commercialization partnership. We are a small company, so we will not launch the product ourselves in the U.S. or other geographies. We are talking to potential partners who will drive that opportunity for us.
Let me start by sharing this. Some of you may be familiar with it, but for those who aren't, this is a good way to understand the unmet medical need that Orviglance addresses. In cancer, liver metastasis is a major problem, meaning cancer spreading to the liver. Many cancer types metastasize to the liver. Around 10% of liver cancers in the U.S. and Europe originate in the liver, called primary liver cancer. Liver imaging is therefore common to stage the disease and assess cancer spread. The best way to examine the liver for cancer is through a contrast-enhanced MRI.
Today, contrast-enhanced MRI uses a gadolinium-based contrast agent. Gadolinium is a heavy metal and is toxic. It is chelated to minimize toxicity and injected into the bloodstream. Orviglance is manganese-based. This is important because gadolinium can cause potentially fatal side effects, known as nephrogenic systemic fibrosis, with the highest risk in patients with severe kidney impairment. Orviglance contains no gadolinium, so this risk does not exist, which is why it has Orphan Drug Designation.
We intend Orviglance to be the product of choice for patients needing liver imaging who have severe renal impairment, because they cannot safely receive gadolinium. The market is an $800 million addressable market, almost half in the U.S. The launch will focus on patients studied in the Phase III trial, where gadolinium use may be medically inadvisable. We will drive commercialization through partners, not through an Ascelia organization .
Looking deeper into the U.S. market dynamics, there are about 100,000 liver imaging procedures for patients with severe renal impairment, within the Orphan Drug Designation and intended FDA label. These patients are very sick and typically treated in large medical institutions, meaning 75% of these procedures take place in the 400 largest accounts.
We have also done extensive work on the commercial opportunity, looking at imaging scan volume and pricing and reimbursement benchmarks, which range from $3,000 to $4,500 per dose for other innovative diagnostics serving small patient populations. We are focusing on the black box warning, which applies to patients with severe renal disease. All gadolinium products have this warning. Other trends in radiology are also important, such as gadolinium deposition after each injection.
It is well established that gadolinium deposits in various tissues regardless of kidney function. Over ten years ago, it was shown that gadolinium also deposits in the brain, a sensitive organ, which requires further research. Another issue is that injected gadolinium leaves the body through urine, entering sewage systems and drinking water. The gadolinium content in drinking water has increased significantly over recent decades.
This trend will continue unless addressed. We are leading the manganese frontier. Orviglance will be the first manganese-based contrast agent, targeting liver patients with severe renal disease. GE HealthCare, a large gadolinium manufacturer, has completed a Phase I study of an injectable manganese version, complementary to our work. Other manufacturers are working on lower gadolinium doses, which reduce exposure but do not solve the problem.
Gadolinium use remains high. This is a dynamic field, and we are happy to lead with manganese and Orviglance. We have advanced Orviglance through development into the regulatory phase, with a PDUFA date on July 3 for FDA approval. We do not have commercial capabilities, so we are seeking a partner to drive commercialization in the U.S. and other geographies. The process is ongoing, and we have multiple conversations. Orviglance is very close to the market, and we hope to get there soon.
We have mapped the commercial opportunity and how this product fits into different companies’ portfolios. This process is ongoing, and we will likely discuss it further during Q&A. The timeline remains: FDA approval expected on July 3. We have everything in place and believe the approval is supported. The NDA includes nine clinical studies, consistently showing efficacy and safety.
Healthy liver tissue is enhanced, making cancers much more visible. Small lesions are more detectable, increasing treatment opportunities. Regarding safety, in these very sick patients, adverse events were mainly mild gastrointestinal side effects, including nausea and diarrhea. Overall, the safety profile is consistent. This is demonstrated in the Phase 3 trial.
On the left, you see an image of a patient. The unenhanced scan is standard practice. Arrows point to tumors, and after Orviglance, healthy liver tissue appears bright, highlighting tumors clearly. Another lesion not visible in the unenhanced scan is now visible, demonstrating Orviglance’s diagnostic value. Three readers evaluated all lesions, scoring each from 1 to 4.
On the chart to the right, we see the Orviglance score minus the score from the unenhanced scan. We observe roughly a 0.6 to 1-point improvement per lesion. This demonstrates very strong efficacy, with a 95% error bar indicating high statistical significance. With this solid data, we are optimistic about a positive FDA outcome. Timeline-wise, we submitted in September, received the Day 74 Letter in mid-November, and expect approval in July. With that, I will switch gears to Oncoral before moving into the Q&A session.
Oncoral is another pipeline asset. It has completed two Phase 1 studies and is an oral formulation of irinotecan. Irinotecan is currently administered as an infusion every third week in hospitals, with very high doses that can cause severe side effects initially. The active metabolite, SN-38, aggressively treats cancer. With Oncoral, we aim to deliver this potent molecule daily, ensuring continuous tumor attack, rather than the intermittent exposure from three-week dosing.
With dosing every third week, the drug half-life means it is gone from the body in a few days. Daily dosing provides continuous tumor exposure, potentially improving efficacy and lowering peak concentrations, which enhances safety. Our goal is to create an irinotecan version with better efficacy and safety. Phase 1 results illustrate this: the gray curve shows high peak concentrations with standard dosing, while the orange curve shows consistent exposure and continuous tumor attack. Safety outcomes were favorable as expected.
No new side effects were observed. Clinical activity included stable disease in very sick patients who previously had tumor growth on IV irinotecan. This is an exciting opportunity. We are starting with gastric cancer. Irinotecan has demonstrated activity in multiple cancer types and is approved for colorectal and pancreatic cancers. For gastric cancer, we plan combination therapy with LONSURF, an approved oral tablet.
The combination of Oncoral and LONSURF would be an all-tablet therapy. Animal studies suggest a synergistic effect of IV irinotecan plus LONSURF, which daily oral dosing could improve. This is a promising opportunity. The IND has been approved in the U.S. I will conclude the presentation before Q&A by highlighting our value creation map and upcoming milestones. Submission occurred in September, FDA acceptance in November, with a PDUFA date on July 3.
This drives Orviglance availability in the U.S. We are preparing launch readiness, manufacturing, and clinical engagement, and ensuring a strong partnership with a commercial team to make the product available to patients and establish Orviglance as standard of care in the target population. Thank you for listening, and I look forward to questions.
Thank you very much, Magnus. We've received quite a few questions.
Great.
Of course. As you might guess, many questions are about licensing deals.
Yeah.
I thought we would start with one of those. Could you walk us through the typical anatomy of a licensing deal, from initial outreach to the data room phase to final execution? Is it common to have contingent agreements triggered by a milestone, like the PDUFA date?
Yes. There are always variants, but generally, for a late-stage asset like ours, after completing Phase 3 with good results and submitting the NDA, we have a comprehensive data room. The best approach is to reach out to as many potential partners as possible. Some may be familiar with the asset, others not. Our goal is to introduce Orviglance widely and generate interest.
We aim to put Orviglance on the map for as many companies as possible. Meetings help R&D teams validate data, while commercial teams assess market opportunity and plan headcount for launch.
Because we are late-stage, the partner needs detailed planning to execute quickly once the deal is signed. This diligence often involves data room analysis, external market research, and ongoing dialogue. There are many steps because we have substantial data and submitted the NDA.
Companies want detailed understanding of the opportunity and risks, and these discussions are progressing well.
A question about your optimistic tone in these discussions: Would you say it is now more a matter of when and the quality and terms of the deal rather than if a deal will happen?
There are no guarantees, but I am very optimistic. We are having serious conversations with senior executives. We expect a deal, though timing and final terms are uncertain. Orviglance addresses an unmet need, has strong data, and presents a strategic opportunity for companies’ portfolios. We cannot control timing, but we are in a good position.
Another question on market research: How do you ensure your research and payer feedback remain relevant approaching the PDUFA date, given analysts may use different assumptions?
I won’t comment on analysts’ assumptions. Over the years, we have conducted extensive market research to develop the best strategy, including pricing, access, and commercial plans aligned with the asset. We avoid strategies inconsistent with the opportunity, as that could backfire.
We also validated initial market research with Phase III data, engaging payers to confirm assumptions about pricing and access. This ensures strong insights to share with partners, whose commercial teams will drive product adoption.
There are going to be many questions on strategy today as well.
Yeah.
On the, on the patent side, manganese itself is an established agent.
Yes
How do you see the patent strategy going forward for Orviglance?
In the U.S., we have Orphan Drug Designation, providing 7 to 7.5 years of market exclusivity. We filed a patent for the food effect study, examining how eating or drinking before dosing affects Orviglance. We also filed a manufacturing patent to improve efficient production and have an issued patent for a second-generation effervescent tablet version.
We believe we have several IP assets and potentially more to protect the Orviglance franchise long-term.
Yes
The core protection remains the seven to seven-and-a-half years of marketing exclusivity from the Orphan Drug Designation in the U.S.
Regarding the U.S. and FDA, there’s a question on the risk profile for a diagnostic contrast agent like Orviglance compared to more complex therapeutic biotech assets. With the regulatory approval process, what are the most challenging points? CMC documentation, pre-approval inspection, manufacturing, or other risks?
Good question. For us, we need to demonstrate consistent manufacture of manganese, with controlled impurities, particle sizes, and other parameters. We have done this successfully multiple times. On the CMC side, we are well covered, with a setup that has strong FDA inspection track records.
On the clinical side, we have nine clinical studies, including a clear Phase 3 result. We believe the risk-benefit ratio is solid. Patients with severe renal impairment face serious risks with gadolinium, but Orviglance, based on manganese, avoids that. Manganese is a natural trace element present in everyone, but Orviglance increases the dose significantly.
This represents a very different risk profile. Overall, Orviglance looks favorable, and for this small patient population, it can make a major difference. We look forward to continuing the FDA process.
Time is running out, so my last question: If we meet in five years, where do you see Ascelia Pharma?
In five years, Orviglance will be fully established as the product of choice in the target patient population, in the U.S. and other geographies. Oncoral will likely have progressed, with a partner in Phase 3 development. Our model is to bring in additional assets. We would mature the existing portfolio while developing and partnering earlier-stage assets efficiently.
We expect a pipeline of four or five assets, several already partnered and some, like Orviglance, already commercial.
Thank you very much, Magnus, for joining us. Thank you everyone for listening.