MSQ’s CEO Webinar Series last week, March 22nd, 2023 focused on the neural exosome platform with Aruna Bio’s interview presentation. Marc Estigarribia moderated with CEO Stephen From and Dr. Steve Stice, CSO, of Aruna Biosciences who both attended to introduce their company and technology. 

Proprietary Neural Exosome Platform for Neurological Diseases

Guest Speaker: Stephen From, CEO, Aruna Bio  

                          Steven Stice, Co-Founder, and Chief Scientific Officer 

Moderator: Marc Estigarribia, Managing Director, MSQ Ventures  

DEVELOPING EXOSOME-BASED THERAPIES: HOW ARUNA PROGRESSED FROM STEM CELLS TO CLINICAL TRIALS 

Dr. Steve Stice started the knowledge-sharing session by introducing the history of Aruna and its drug development. He had always been intrigued over the years by the idea that neural stem cells could introduce material innovative therapeutic opportunities. However, the mechanism of action and the route of administration inhibit the use of stem cells for many neurological diseases. “It was about 6 years ago that we came upon the idea that maybe it's not the stem cells themselves, but actually what the stem cells produce”, he said. Finally, they devoted time to studying the exosomes of stem cells and succeeded in progressing to the clinics today.

FUTURE ADVANCEMENTS AND CLINICAL APPLICATIONS OF EXOSOME-BASED THERAPIES: PROPRIETARY CELL LINE AND TRANSLATION FROM LAB TO CLINIC 

Furthermore, Dr. Steve Stice accounted for the breakthroughs in the next 3 to 5 years. As years of evolutionary pressure have made exosomes very useful, “I don't see us being able to improve on the native form of exosomes tremendously, but how we use them in the future or in the clinics, as well as is moving on to different indications are really going to be important advances”, he concluded. 

Mr. Stephen From, CEO of Aruna Bio answered the question about the relationship between basic research and clinical transformation. He said, “We're taking it from the lab into the clinic to treat patients with the product”. Compared to other companies using generic cell lines, Mr. From emphasized that their advantage is their proprietary cell line, which is able to produce a therapeutic axis zone without any modification or engineering of that cell or of that axis zone. “We're excited to get this into the clinic.” 

UNLOCKING GLOBAL POTENTIAL: ARUNA’S AB126 WITH BBB-CROSS CAPABILITY AND MULTIPLE MODES OF ACTION FOR COMPLEX NEUROLOGICAL DISEASES 

Mr. From finally elaborated on their global expansion aspirations including global-regional collaborations. As Aruna is a small company with limited resources, they don't have the ability, expertise, and resources to take their product outside of the US. Thus, “we'd be looking for a partner that actually has that expertise”, Stephen remarked, to take the product into the market or even into the clinic to treat stroke or TBI or chronic neural degenerative diseases. 

In the formal company presentation, Mr. From first introduced their main product AB126, an unmodified exosome with the ability to cross the blood-brain barrier (BBB) and facilitate tissue repair with its regenerative properties. Mr. From noted that their first IND submission is anticipated in Q3 2023, with phase 1b safety study in stroke patients. They had access to a pig model to validate how their product works in an extreme stroke environment and raised over $5 million from NIH to make sure their product received an IND file. Besides, they have their own GMP facility.  

Mr. From emphasized the significance of their AB126 being able to cross the BBB. As both acute and chronic diseases have an inflammatory response, it is important to get across the BBB to modulate that immune response and facilitate tissue repair. “It's important to understand that crossing the blood-brain barrier is of utmost importance no matter the therapeutic effect. You are not going to have the opportunity to use it”, he said. In addition, AB126 are enriched in miRNAs involved in neural stem cell proliferation and differentiation, as well as neural survival, myelination, and angiogenic properties, so that they can use a multi-modality approach for complex diseases. Mr. From and Dr. Stice then presented data using TBI Porcine Model to prove that their AB126 can modify the immune response and translate that into mitigation of tissue damage, lesion size, and atrophy. Besides, AB126 has the potential for treating ALS and Vascular Dementia. Finally, Mr. From underlined that they have different patent families for this first product family both in the US and Japan and pursuing it in China. “We are excited to bring on a partner that can help us with our development”, he added. 

During the Q&A session following the presentation, Mr. From and Dr. Stice discussed the prospects for the industrialization of exosomes, the safety concerns of exosome treatments, and the potential for AB126 in the field of neurological disease. They also discussed future development plans for AB126, and its potential in the field of neurological disease and furthermore as a carrier in combination with other therapeutics, and its potential effectiveness for both ischemic and hemorrhagic strokes. Additionally, they expressed interest in expanding disease indications for exosome treatment beyond vascular dementia and motor neuron diseases to include all forms of dementia. They highlighted the uniqueness and effectiveness of their product and the vast number of diseases or conditions that could be treated as a result. 

At the end of the webinar, Mr. From reiterated the uniqueness and effectiveness of their product. Because of the robustness of their preclinical package, a huge number of diseases or conditions could be treated. The opportunity is huge. 

Q&A HIGHLIGHTS 

Q1: Exosomes still face challenges in large-scale industrial production. The commercialization approval of exosomes is relatively complicated. How do you view the prospects for the industrialization of exosomes? 

A1: Mr. From explained that they put a lot of effort and resources over the last 3.5 to ~4 years to really make sure and fine-tune their process. “It is a difficult area, and that's why we've taken it on ourselves”, he said. Fortunately, they’ve made leaps and bounds as to how pure and how much they can collect of the exosomes just even over the last 12 months. With this technique, Mr. From thought it was going to be applicable for scaling up to get into the later stage right now. Dr. Stice added that they moved to multiple levels of filtration and chromatography and so forth to be able to scale this not only on the manufacturing side but also in making sure it is a pure product as clean as possible for use in the clinical area. 

Q2: What is the major safety concern of exosome treatments? And how do we mitigate that risk? 

A2: Compared with a foreign body like a lipid-based nanoparticle bringing toxicity issues to our immune system, exosomes coming from cells do not cause any problem with the toxicity or immune reaction. “Exosomes are natural and that keeps them from triggering an immune response when introduced into humans”, Dr. Stice concluded. 

Q3: What unmet clinical needs do you think AB126 has the potential to meet in the field of neurological disease? 

A3: Mr. From commented that it is still unknown why the human body produces exosomes to compensate for injuries. However, AB126 can facilitate tissue regeneration without knowing what caused the problem. “But again, other companies, even the larger ones, are really not doing what we wanted to do”, he said. 

Q4: What about your future development plans for AB126 in the next 3-6-9 months including upcoming milestones? 

A4: Mr. From pointed out that their first product would have several important milestones. They will use this agnostic approach to keep building a larger pipeline and assume that it is working in the clinic for the acute and the chronic conditions. Another exciting notable is that exosomes can be used as carriers. “Our next product for AB126 could be a combination with another therapeutic”, he concluded. 

Q5: Can we expect the same effect of AB126 for both ischemic and hemorrhagic strokes? 

A5: Dr. Stice remarked that even though there is no treatment for hemorrhagic strokes right now, there is an innate ability of exosomes to have an effect on vascular cells, on the end of the allele cells, and the spoon muscle cells that are surrounded in the arterial function. As a consequence, exosomes can make the brain less leaky and start with repairing after a hemorrhagic stroke to decrease the chances of stroke. It is both an opportunity and a challenge. 

Q6: Does the exosome treatment have a treatment time window similar to tissue plasminogen activator tPA? 

A6: Dr. Stice noted that AB126 could actually act as a protective in combination with a thrombectomy or mechanical removal of the blood clot. “They are not acting in the same way, so it is a perfect opportunity to combine treatments and have a beneficial effect beyond the tPA or from activities”, he summarized. Mr. From added that once the safety studies are completed and they have an open IND, they can try different things for stroke patients. “We can push the boundaries more and more with different populations within the stroke area and it would be exciting to try that”, he noted. 

Q7: Do you have plans to extend the indication of diseases such as Parkinsons’ Disease (PD) and Alzheimer’s disease (AD)? 

A7: Mr. From agreed that they are the first ones to get these two done. “But there is no reason why this (exosome) should not be applicable to all forms of dementia, not just vascular dementia and motor neuron diseases”, he remarked. However, he emphasized that they need more resources to support them.