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Mark Gergen, Poseida Therapeutics’ President and Chief Business Officer, talks to Pharm Exec about the efforts underway to develop effective, safer and more accessible treatments for patients with cancer and rare genetic diseases and outlines his company’s commitment to make single-treatment cures a reality.
Pharm Exec: How are Poseida’s CAR-T product candidates advancing cell therapy to improve cancer treatment, and how do you see them impacting the current landscape?
Mark Gergen: Poseida’s genetic engineering tools provide a scientific foundation for developing safer, more durable, and more efficacious treatments, with the goal of achieving single treatment cures available off-the-shelf for patients with cancer and genetic diseases. Existing solutions in cell and gene therapy have limitations and, in some cases, serious safety liabilities. Our company is positioned to create potential cures with better safety profiles due to our differentiated technologies and unique approach.
Our technologies offer several advantages, starting with our piggyBac® DNA Delivery System, a non-viral platform technology that allows us to deliver a product with a high percentage of stem cell memory T cells (or Tscm), which are the ideal cell type for T cell therapy. We believe this Tscm cell type is the key to durability and safety, particularly in solid tumors. In gene therapy, piggyBac is an integrating technology so the gene correction is permanent and stable – enabling potential single treatment cures unlike most other approaches that use older virus-based systems.
What are the advantages of Poseida’s nanoparticle delivery approach over traditional adeno-associated virus (AAV) delivery for gene therapy?
We’re developing proprietary biodegradable nanoparticle technology to enable potential single treatment cures for patients, many of them infants and children, affected with severe and difficult-to-treat genetic diseases. With our non-viral nanoparticle delivery technology, we avoid many of the challenges, limitations and safety concerns that are seen with AAV delivery. Our nanoparticles, together with piggyBac, allow us to deliver larger genes, re-dose or dose titrate and treat juvenile populations that AAV or RNA approaches cannot effectively treat. These genetic mutations are permanent, so if you have a non-integrating technology like AAV, or if you're delivering RNA with nanoparticles, you have a temporary treatment, not a correction or cure of the disease. This is a primary differentiator for us among our competitors in gene therapy.
How do you determine which development programs to prioritize when your gene engineering technologies have such broad potential for treating cancer and genetic disease?
We made the decision to start with CAR-T for oncology because ex vivo applications of our technology were more straightforward and we had numerous advantages over others in the space. In parallel with pursuing CAR-T, we also advanced our nanoparticle technology to enable non-viral in vivo liver directed gene therapies.
In CAR-T cell therapy, we are focused on allogeneic, or off-the-shelf, products but believe that a key to developing successful CAR-T has been to do deep learning with autologous CAR-T cell therapies. Our two autologous candidates currently in the clinic are P-BCMA-101 for relapsed/refractory multiple myeloma and P-PSMA-101, a solid tumor target for castrate resistant metastatic prostate cancer. This year we are planning INDs for two fully allogeneic CAR-T cell therapies: P-BCMA-ALLO1 for relapsed/refractory multiple myeloma and P-MUC1C-ALLO1, a pan solid tumor target.
Our initial gene therapy programs are focused on treating diseases including Hemophilia A and Ornithine Transcarbamylase (OTC) deficiency, two significant unmet needs – especially when focusing on the juvenile patient populations. When selecting these and other indications, we focus on high unmet medical need and patient populations that cannot be treated effectively with other approaches.
For example, in the case of OTC deficiency, there are few approved treatments, and they are expensive and not completely effective. Liver transplant can be curative, but it is not broadly available and is fraught with high cost and high risk. We know that we have a competitive advantage in the pediatric population because other transient gene therapies will not work – in part because the liver cells in infants are rapidly dividing and, if you do not integrate your treatment into the DNA, it will get diluted out as cells divide.
In the face of new treatments emerging in the space, what is your vision for Poseida’s future?
Our goal is to develop therapies that will cure disease rather than just treat them. Our genetic engineering technologies are highly differentiated, and we plan to focus on developing them where that differentiation can benefit the most patients. Due to the breadth and utility of our technologies, we know we cannot develop all the applications ourselves and so partnership and strategic collaboration are key pillars of our strategy.
While early cell and gene therapies have shown promising results, more innovation is needed.In our view, older tools and approaches like viral-based technologies are not capable of unlocking the substantial promise of changing the standard of care with cell and gene therapies.
What drew you to Poseida and what fuels your motivation as President and Chief Business Officer?
I have worked in the healthcare industry for more than 25 years and have never seen a company with as many unique and broad technology platforms as we have here at Poseida. Moreover, most companies that I am aware of in this space have one technology or approach, while here we have all the tools needed to pursue gene insertion, gene editing and gene delivery for cell therapy or in vivo gene therapy applications. We are, in a sense, a platform technology holding company with many, many opportunities before us that can be enabled and pursued.
All of that technology and potential opportunity present a great strategic challenge for the company and for me. How do we effectively and efficiently develop all this technology to unlock value for our stakeholders and patients? The opportunities to develop the many therapies and expand patient access to potentially life-changing cell and gene therapies are too broad and deep for us to do alone. That is why we are open to and actively seeking collaborators to leverage the power of our platform technologies in new and innovative ways.
What would you say is unique about the culture at Poseida?
Our team thrives on creativity, disruptive thinking, scientific advancement, collaboration with each other and academic and strategic partners, and our shared cultural values of passion, innovation, and nimbleness. As we focus on our vision to enable single treatment cures using our unique genetic engineering technologies, we need to be not only agile, but also adaptable and innovative. We are using, and constantly developing, new technologies, approaches and solutions to find breakthrough scientific advancements to pursue our vision. The status quo is not adequate and using old technologies that are not really fit-for-purpose is not acceptable to us.All of these factors energize us and are key to Poseida’s culture as we work to change the future of cell and gene therapies.
How do you see the fields of cell and gene therapy evolving in the future?
Ultimately, we need to see a move away from transient therapies, and as an industry, address safety and durability and create more affordable treatments that work for the broader healthcare ecosystem. AAV, Lentivirus and other virus-based technologies are old and not well fit for these applications. We need to accelerate innovation with the goal of creating next-generation cell and gene therapeutics with the capacity to cure with a single treatment. For patients and their families, that is the future.