In this presentation, Xiaokui Zhang, Chief Scientific Officer of Aspen Neuroscience, provides a comprehensive update on the company’s autologous induced pluripotent stem cell (iPSC) platform aimed at treating Parkinson’s disease and other central nervous system (CNS) disorders. He outlines the company’s origins in Dr. Gene Loring’s Scripps lab, the vision to create highly characterized pluripotent‑derived cell medicines, and the formation of a patient‑focused team in 2018. Zhang details the completed IND‑enabling studies for the lead product AMPD001 (autologous iPSC‑derived dopaminergic precursors), the launch of a trial‑ready patient cohort, and the design of a Phase 1/2a safety and dose‑response trial that incorporates PET imaging and functional readouts. He highlights a 22,000 sq ft GMP manufacturing expansion, the integration of AI‑driven genomics and machine‑learning quality‑control pipelines (pre‑test, neurotest, whole‑genome sequencing, RNA‑seq) that de‑risk the product and reduce cost. A landmark preclinical study published in Nature Biotechnology, comparing autologous versus allogeneic dopaminergic precursors in non‑human primates, is presented as validation of the approach, showing superior motor and non‑motor outcomes. Zhang discusses the unmet need in Parkinson’s disease, the rationale for cell replacement of lost substantia nigra dopamine neurons, and the broader pipeline exploring additional CNS cell types and extra‑CNS indications. The company’s recent $147.5 M Series B financing, backed by marquee investors, is announced, and Zhang invites collaborations to accelerate development. The talk concludes with a reaffirmation of Aspen’s vision to be the leading autologous iPSC‑based therapy developer.
Chapters
Thank you so much. Can everyone hear me okay back there? Great. Good morning to all. It's very exciting to be here, and thank you for the organizers for this great opportunity to be here. I'm very excited to provide the update of what is going on at Aspen Neuroscience. It's a great opportunity for me to talk about this transformative iPSC cell therapy, which is autologous approach in the neuroscience Space. Just need to navigate this a little bit. Great. This is a company that formed on the vision to create the best characterized pluripotent-derived cell medicines. And we came out of Dr. Gene Loring's lab at Scripps Research Institute where 20 years of award-renowned stem cell research and the cutting-edge genomics. That being created there. And Gene and the co-founder, Andres Bernalillo, that co-founded the company in 2018 and joined by a group of research scientists from Gene's lab and a group of patient advocates from Summit for Stem Cells. So this is a company that formed for the patient. We highly differentiated with a disruptive iPSC platform technology. And our approach is autologous, which is the ultimate personalized medicine for every patient. So since 2018, we have built an exceptionally experienced management team and a great visionary board of directors. So I'll elaborate some of the details on the pipeline, our Series B funding, and also the manufacturing build-out. Over the next couple slides. So in short, our vision is to be the leading autologous cell therapy company. So how do we do that? Aspen has spent years to build the foundational technologies for our platforms. So at the heart of the core is really the AI-based genomics to inform stem cell biology. Since inception, we have built and will continuously expand and augment our in-house manufacturing and the quality system. Systems. We have incredibly innovative to improve and optimize neurosurgical procedures to ensure delivering of the cell therapy in a safe and precise manner to the specific region of the brain. So we're starting with the first indication in Parkinson's disease, and then we're looking at other areas in the CNS space and very actively looking on the pipeline build-out. And beyond the CNS in the near future. 2022 has been a really great year and big year for the company. Now we consider ourselves to be a clinical stage Series B company. Early part of the year, we have completed all the IND enabling studies, including safety talks and the efficacy, and plus all the CMC activities. For the first product named ANPD001. So those are the studies required for the IND submission. We are opening our trial-ready cohort studies as we announced several months ago. So we're screening patients and ready for the initiation of the clinical trials. We have completed our significant footprint expansion by acquiring additional 22,000 square feet to continue our GMP manufacturing expansion and augmentation all the way that we believe to the Phase 2B. We're thrilled to close our Series B round of $147.5 million with, with a group of marquee investors backing us up. We're very excited about this. So not to belabor this audience with Parkinson's disease, just to highlight, currently there is still no disease-modifying agent on the market. Even with the current standard of care, patients eventually develop the debilitating motor complications, which is devastating and affecting their quality of life. The economical burden is humongous, that huge burden not just to the patient, also for the the caregiver, and the society because of this degenerative disease affecting millions of the patients worldwide. So this is Aspen approach. So through decades of the study of the disease that we understand that this neurodegenerative disease is caused by loss of the dopamine neuron that's residing in this part of the midbrain. Called substantia nigra. At the diagnosis, typically more than 50% of the dopamine neurons are already lost. So Aspen is developing a cell replacement therapy with the goal that we deliver those cells in a safe and precise manner to the specific region of the brain to replace the lost dopamine neurons and potentially for those cells to reconstruct the neural circuit then in order to reverse some of the Parkinson's symptoms. So this is our approach. And this approach is actually backed and supported by the years of the experience utilizing fetal tissue-derived cell therapies, which is summarized in the next slide. So this is the experience and studies that started in the 1990s. Then even though there are There are some variable results and the outcome from the study that we actually see some of the observations that in patients, especially the durable long-term benefit and clinical outcome to be really de-risking for our approach, which has the huge potential. The next slide actually summarize a really high level of the overview of the current process that's being utilized to derive the first product called the AMPD001, which is autologous iPSC-derived dopaminergic precursor cells. We started with a patient biopsy and then followed by the disassociation to derive dermal fibroblasts, then followed by the reprogramming to iPSC clones. And some of the clones will pass the QC filtering for the subsequent differentiation to yield AMPD001. And the folks in the audience know that making iPSC cell products, it's not easy. It's really hard. So we integrated created a very extensive QC matrix and filtering system, including pre-test and the near test. Those are the AI-focused machine learning algorithms to predict the fate, the quality, and potentially the safety of the product throughout the manufacturing process. Here is a little bit more details into how we're actually conducting such quality controls throughout the manufacturing. So in addition to the pre-test and neurotest, we also conducted the other, the genomics tools, which are the whole genome sequencing, single nucleotide polymorphism, which is also the digital karyotyping that we utilized, and the integrated, and also the gene expression, the sequencing RNA-seq. That's throughout the process to ensure the cells are free of the tumor driver mutations or any other potential detrimental genetic genetic alterations. We believe the approach that we're utilizing at Aspen that ensure the safety and the efficacy and replace some of the costly animal studies such as the pretest, which is machine learning algorithm to predict the prepotency of the iPSC clones, and the neurotest, again, is a machine learning algorithm to ensure the identity and determine the differentiation state of the AMPD001 at the end of the production. So this could really potential— potentiate the reduction of the cost and the time of the manufacturing process. So before I talk about the clinical plan, I just wanted to revisit this really landmark publication from our collaborator, Dr. Marina Amber, published last year at the Nature Biotechnology. So this is one of the longest nonclinical study in the hemiparkinsonian non-primate models to evaluate and compare and contrast autologous versus allogeneic dopaminergic precursors for safety, efficacy, and durability. So as you can see from the graph at the lower right corner, the blue The blue groups are the autologous groups, which have shown the significant advantages and the improvement in terms of motor function, which was correlated with IHC studies of the fiber outgrowth from those grafts and also the durability of those engraftment throughout the period of the time of the evaluation and also the PET imaging was actually shown to be very predictive of the functionality and also some of the long-term engraftment effect as well. And this is a study also revealed for the first time some of the non-motor improvements such as the mood of the monkeys and also the self-harm being reduced. So really, really encouraging for us. So all in together. So we felt that study really validated our approach to use autologous dopamine neurons and also provided the additional, the sort of a fruit for further evaluation, established additional translational correlates, and build that into our clinical plan. So just, this is actually the current clinical trial plan. And as I mentioned earlier, we have started our cohort, the studies, the trial-ready cohort study to start screening for the patient, which is agreed upon with the agency at the pre-IND meeting. And it was basically a way to initiate the IND filing, the submission to the agency, and to potentially accelerate the clinical development by pre-fill the pipeline for manufacturing. The primary objectives of our Phase 1/2a study is to focus on the safety, tolerability, and dose responses. So we also have built in the PET imaging, as I mentioned in Marina's paper, to be very correlative to the function and additional clinical readouts so we can learn and capture the evidence of the biological effects and the activities for the ANPD001. And the other informative evidence so that we can further plan for the Phase 2b clinical trial. Just very quickly to touch upon the pipeline development at Aspen Neuroscience, we're very excited for this area that, as I mentioned, so there are multiple programs that are being built out and currently we're pursuing very active research to evaluate the multiple cell types that within the CNS beyond Parkinson and also beyond the CNS. We're actively looking for the partners and the collaborators to synergize this effort to potentially accelerate the development. So just to quickly to mention some of the approaches that being integrated into the research and development at Aspen. So learn from the field over the decades of developing the cell therapy, it is important to again the quality of the design in the early stage of the development. So we've been utilizing the systematic analytical tools such as a factorial experiment design to generate the data that understand the inputs and the outputs. And with all the data that being further utilized to train the machine learning algorithm being established and started in James Lawrence's lab, we have learned a lot how to understand, how to establish the process, and followed by the further optimization. And with the goal to really come up with a model prediction systems to ensure that not only the good quality of the product and also the product with the critical quality attributes that are desired for the specific indication can be produced through this efforts. And in parallel, we're working really hard to identify those potential technologies that would enable us to establish a fully enclosed manufacturing automation. So there are several members of the leadership that are in the audience. We're actually very excited to talk to, to meet with the folks who are interested in our technology and the platform to explore the potential collaboration and the partnership to help us to accelerate these efforts. Just to end my presentation on the vision again, we're the company with a vision to be the best developer of autologous iPSC-based therapy. Our approach is to bring the datasets to bear, understand it and identify the mechanisms and the platforms to further improve and de-risk that for multiple programs and starting in Parkinson's. And then we wanted to ensure this competitive advantage that we have established at Scripps and further extended at Aspen can be strengthened through the effective and synergistic partnership and the collaboration. We believe that personalized medicine starts with you, and patients are waiting. With that, I want to thank the audience for your patience and see if we have the time for questions. 30 seconds. Okay, thank you.
