Abarceo Pharmas vd om teknologin och kommande milstolpar

Abarceo Pharmas läkemedelsutveckling går ut på att återställa mitokondriell hälsa, med ett initialt fokus på typ 1-diabetes. Vid typ 1-diabetes kan patienterna inte producera tillräckligt med insulin för att möta kroppens behov, vilket beror på att immunceller attackerar våra insulinproducerande betaceller. Attacken är särskilt aggressiv hos barn upp till sex års ålder, där den dödar de flesta betaceller. Om sjukdomen utvecklas efter sex års ålder är immunangreppet ofta mildare och en hel del betaceller överlever. Dessa celler hamnar dock i ett slags ”viloläge” där de inte svarar som de ska vid måltider.

Visserligen kan patienten få konstgjort insulin, men inget slår kroppens eget eftersom det ger en bättre kontroll av blodsockret. Vid typ 1-diabetes är detta avgörande, då även små mängder egenproducerat insulin förebygger diabeteskomplikationer i ögon, njurar och hjärta. Bolagets mål är därför att återställa betacellerna från ett dysfunktionellt till ett fungerande tillstånd, så att patienterna kan börja producera sitt eget insulin igen.

Förståelsen för mitokondriernas roll vid diabetes

Abarceo grundades 2017 som en avknoppning från Lunds universitets diabetescentrum, av professor emeritus Claes Wollheim och docent Albert Salehi, två världskända forskare inom diabetesforskning. De har ägnat sitt arbete åt att förstå en av de underliggande mekanismerna vid diabetes: mitokondriell dysfunktion i betaceller, vilket orsakar nedsatt insulinproduktion.

Grundarna var först med att beskriva att metabolitkanalen VDAC1 är en del av problemet vid typ 2-diabetes, vilket öppnade för ett helt nytt angreppssätt för behandling av sjukdomen. Proteinet VDAC1 sitter i det yttre membranet på mitokondrierna – ”cellens kraftverk”. I vissa celltyper, såsom betaceller och nervceller, finns VDAC1 även i cellmembranet. VDAC1 är ett uråldrigt protein vars struktur och funktion har bevarats i hög grad från jästsvampar till människor. Det reglerar flödet av den energibärande molekylen ATP ut från mitokondrierna till cytoplasman, vilket förser cellen med energi.

Vid diabetes leder det höga blodsockret (hyperglykemi) till ett överuttryck av VDAC1, oligomerisering (klustring av molekyler) och att proteinet felaktigt söker sig till cellmembranet. Detta resulterar i att ATP läcker ut ur cellen, vilket stör insulinutsöndringen. Detta ATP-läckage tros vara den bakomliggande orsaken till de ”sovande” betacellerna, som saknar energin för att utsöndra tillräckliga nivåer av insulin.

Vill återställa cellernas funktion

Abarceo Pharma siktar på att täppa till denna läcka och återställa betacellernas normala funktion hos diabetespatienter genom att hämma det dysfunktionella VDAC1, både i mitokondrierna och i cellmembranet. Detta skulle enligt bolaget kunna ge en effektiv och hållbar kontroll av sjukdomen. Data från studier på donerad vävnad från diabetespatienter, samt diabetiska möss, tyder på att blockering av dysfunktionellt VDAC1 kan återställa både insulinutsöndringen från betacellerna och insulinkänsligheten i lever-, muskel- och fettceller.

Man har även sett lovande resultat för metoden i sjukdomsmodeller för Alzheimers och hjärtsvikt. Mitokondriell dysfunktion och energiförlust är kopplade till en rad åldersrelaterade sjukdomar, inklusive hjärt-kärlsjukdomar och neurodegenerativa sjukdomar. Tillsammans utgör dessa mångmiljardmarknader där det finns stora medicinska behov som ännu inte tillgodosetts.

Läkemedelsutveckling i samarbete med Big Pharma

Abarceo Pharma fokuserar nu på lead optimisation, det sista steget i forskningsfasen, med målet att välja ut läkemedelskandidater för diabetes och potentiellt även för andra indikationer. Utöver den interna utvecklingen samarbetar bolaget med både Eli Lilly och Biogen för att ta fram behandlingsalternativ. Samarbetet med Eli Lilly fokuserar på utveckling av monoklonala antikroppar mot VDAC1, medan samarbetet med Biogen inriktas på att utveckla småmolekyler som hämmar oligomeriseringen av VDAC1.

Vd kommenterar

Bolaget förväntar sig snart en första uppsättning proof-of-concept-data från en pågående preklinisk studie, där förhoppningen är att se tecken på återställd insulinproduktion – likt det man sett i pankreatiska öar från diabetespatienter. BioStock kontaktade VD Adam Bruce för att höra hans tankar kring detta och ta del av hans vision för Abarceo Pharma.

You are initially focusing on type 1 diabetes. What does this patient group look like today?

– We are specifically targeting a subgroup of patients with a young adult-onset type 1 diabetes. Traditionally, type 1 diabetes is often associated with childhood onset, but there is a growing and well-defined group of patients who are diagnosed later in life, at around 18 years of age.

– This group represents a significant unmet medical need. Frequently, they are misdiagnosed as type 2 diabetes. Furthermore, type 1 diabetes is increasing globally, with notable rises in regions like the Middle East and even here in Sweden. Targeting adults also offers strategic advantages for clinical development, as compliance tends to be higher and the safety profile is generally easier to manage in fully developed bodies compared to children.

Given that focus, what does the current treatment landscape look like for these patients, and what would your technology potentially add?

– The treatment landscape has remained largely unchanged for a century, relying almost exclusively on insulin. While there have been significant advancements in monitoring and delivery systems—like sensors, apps, and pumps—patients are still burdened with managing their glucose levels around the clock.

– Insulin therapy comes with its own drawbacks. If you inject too little, the patient can undergo ketoacidosis due to constantly high blood glucose. If you inject too much, then the patient can undergo hypoglycemia.

– Both these potentially life-threatening episodes further deteriorate the health of existing beta cells. Therefore, what we are aiming for is fundamentally different: a once-daily pill that could potentially restore the body’s own ability to regulate insulin. Instead of just managing symptoms, we want to wake up the ”sleeping” beta cells. If successful, this would be a standalone product that could drastically reduce the burden of the disease.

Sanofi’s Tzield recently received market approval in Europe, and your Swedish collague Diamyd is in phase III. How do you view the competitive landscape, and where does Abarceo fit in?

– It is encouraging to see movement in the field with products like Tzield reaching the market. However, these are immunotherapies designed to delay the onset of the disease by a few years, and they often come with high costs and complex administration requiring hospitalization for a few days.

– Our approach is distinct because we are targeting the underlying mitochondrial dysfunction with a small molecule. We aim to offer a more accessible, cost-effective, and patient-friendly oral treatment that not only halts disease progression but potentially restores function. We see ourselves as offering a unique mechanism of action that could be a powerful alternative or complement to these immunotherapies.

You mention this as a potential standalone product, but could it also work in combination with existing treatments?

– Absolutely. While we are developing a standalone product that should be able to stand on its own, there is a definite potential for combination therapies. For instance, our treatment could complement the entire range of existing options, from GLP-1 agonists to emerging vaccines or immune-modulating therapies. By supporting the system with two different mechanisms, you could potentially achieve even better control and outcomes for patients.

With the broad applicability of this technology, can you elaborate on why you decided to start with type 1 diabetes?

– We chose type 1 diabetes, and specifically a subgroup of adult-onset patients, for several strategic reasons. First, there is a massive unmet medical need. Second, this patient group is well-defined, and we know that these young adults generally have better compliance with medication. From a safety perspective, targeting adults whose bodies are fully developed also reduces risk compared to treating children.

– Furthermore, this approach allows us to pursue an Orphan Drug Designation. This regulatory pathway offers significant advantages, including the potential for fast-track status and earlier approval. Our plan is to first demonstrate safety and efficacy in young adults through phase I and phase IIb studies, secure market approval, and then expand into paediatric populations and potentially other indications.

Given the promising data in other indications like Alzheimer’s and heart failure and the need to focus as a smaller company, how do you view the potential expansion into these areas, and what would trigger such a move?

– The platform potential is definitely there. We have seen that the mechanism of VDAC1 dysfunction is relevant in other conditions where inflammation disrupts mitochondrial energy metabolism. However, for a company of our size, focus is critical. We cannot chase every opportunity at once.

– We have prioritised type 1 diabetes because the medical need is acute and the innovation in the field has been sparse. That said, if we secure the right funding or partners, the door is open to explore these other indications. Ideally, we would like to see Abarceo grow into a fully integrated pharmaceutical company that can take products all the way to market, similar to a journey like Hansa Biopharma.

You have established collaborations with major players like Eli Lilly and Biogen, while also working with expert partners for your chemistry development. How do these different external partnerships complement your in-house efforts to select a lead candidate?

– These collaborations are invaluable. We conduct our chemistry development with an expert external partner who guides us in selecting the right candidates that can pass our rigorous screening systems. Developing the right assays to evaluate these molecules against our specific target has been challenging and time-consuming, but we are now very close to selecting a lead candidate.

– Having partnerships with industry leaders validates our approach and expands our capabilities, giving us multiple shots on goal as we move forward.

This fall, you expect the first proof-of-concept data from an ongoing preclinical study—what specific outcomes regarding restored insulin production do you hope to see, and how will you validate these results before advancing to clinical phases?

– We are currently running a study in a specialised animal model for type 1 diabetes in collaboration with a Spanish academic institution. What we are looking for—and what we have seen early signs of—is to keep the animals non-diabetic, thereby implying better survival of functional beta cells.

– Crucially, it appears our treatment may prevent the autoimmune attack from setting in, effectively protecting the beta cells before damage occurs. This is a very exciting development. We have received very positive initial reports, and we are now in the process of analysing the full data set to confirm these findings.

As CEO, what is the biggest uncertainty in your development right now, and how are you managing it?

– The biggest uncertainty, as for any biotech company in this phase, is always financing. If you wake up a single day without hunting for money, you aren’t doing your job. We mitigate this risk by being extremely active—attending conferences, meeting investors, and constantly telling our story.

– The good news is that the sentiment seems to be shifting. Investors are sensing ”morning air” again, and there is renewed interest in the sector, especially for companies with high-potential assets like ours. We are constantly working to ensure we have the resources to take our lead candidate through the necessary preclinical toxicology and safety steps to reach an IND filing within the next 18 months.

Once you achieve the complete data set in preclinical proof-of-concept, what is the logical next step for capital raising?

– We are open to various paths. We have existing collaborations, and if a partner presents an offer that aligns with our strategic goals and valuation, we would certainly consider it. We are not locked into a single strategy of doing everything ourselves if a better option for the company and shareholders arises.

– However, our primary plan is to raise the capital needed to take our lead candidate into the clinic ourselves. We see a clear path to generating value by reaching clinical proof-of-concept in humans.

Apart from the results, what milestones are you looking forward to in the next twelve months?

– The next big step is taking our selected lead candidate into formal preclinical development—tox studies, PK studies, and everything required for regulatory submission. Our goal is to have a IND in place in about 18 months.

– After that, we plan to initiate a phase Ia/Ib study, which will take about a year, followed by a larger international phase IIb study. So, the immediate focus for the year is rigorous preparation to ensure we enter the clinic with the best possible chances of success.