Allogene Therapeutics is a clinical-stage biotechnology company developing allogeneic chimeric antigen receptor (CAR)T-cell products for cancer and autoimmune disease.
Zach, you have a rich experience in the life sciences industry. What made you join Allogene Therapeutics specifically?
Allogene Therapeutics caught my attention from its inception. I knew its founders and some executive team members from our time at Kite Pharma. The allure was the groundbreaking potential of allogeneic, or “off-the-shelf”, CAR T-cell products, a modality I believe is essential for broadening the reach of this life-saving treatment. Despite the honor of being part of the pioneering team to receive FDA approval for one of the first CAR T-cell therapies for cancer while at Kite, it was clear the accessibility of such treatments needed to be expanded. So when the opportunity to join Allogene as the head of R&D presented itself in late 2022, I jumped at the opportunity. I had seen some recent updates on Allogene’s clinical programs showcasing the company's promise and progress in a way that aligned with my hopes for the future of CAR T.
Could you explain the basis of your technology and the significance of allogeneic Chimeric Antigen Receptor (CAR) T-cell products?
Current CAR T development has been primarily defined by how autologous CAR Ts are made and used today. While these therapies were a breakthrough in the treatment of cancer, logistical and infrastructural challenges, as well as access to treatment, have limited the number of patients who have been able to benefit from this modality. We’re developing CAR T with a focus on the inherent benefits of an allogeneic or “off-the-shelf” option, that can be readily available and delivered much more broadly than autologous CAR T today. Allogeneic CAR T products are developed using T-cells from healthy donors. These cells are isolated in a manufacturing facility, engineered to express CARs to recognize and destroy disease, and modified via gene editing to limit autoimmune response when given to a patient. These products are then stored for “off-the-shelf” use on demand. This is a contrast to autologous CAR T-cell therapies that are developed using cells derived from patients that require a bespoke manufacturing process. Our allogeneic approach is designed to allow for the production of more than 100 doses from a single manufacturing run, significantly scaling up access to CAR T.
Allogene currently manufactures its cell products in-house. Do you plan to continue this as you scale?
Rather than outsourcing, Allogene is centralizing and expanding its own manufacturing capabilities. When we first formed, we used contract manufacturers in order to get into the clinic quickly, but immediately focused on building our own in-house facility to internalize the production process. This strategic shift enables greater control over the quality and availability of our products. We plan to produce all of Allogene's cell products in-house, reinforcing our commitment to delivering these groundbreaking products at scale.
Is your manufacturing process automated? How do you resolve the challenge of manufacturing speed?
The manufacturing of our investigational cell products involves a combination of automated and manual processes. The challenge of manufacturing speed and efficiency is particularly significant for autologous CAR T manufacturers, where the individualized manufacturing process necessitates rapid production and delivery to treat patients with rapidly progressing cancers. However, as an allogeneic CAR T manufacturer, this issue is less critical for Allogene. Our product candidates are produced in advance, stored, and ready for immediate administration, which should drastically reduce the time from patient eligibility to treatment commencement. This efficiency is a key advantage of allogeneic over autologous therapies, ensuring timely treatment without the constraints faced by a patient-specific manufacturing approach.
Could you provide an overview of your current pipeline?
Allogene's pipeline includes a multitude of investigational products, but we are highly focused on four cell therapy programs in particular. Our lead program, cema cel (ALLO-501A), is a CD19-targeted CAR T product that has shown promise in Phase 1 clinical trials. We are advancing this investigational candidate in two clinical trials – ALPHA3 in first line (1L) consolidation for large B-cell lymphoma (LBCL), and ALPHA2 for relapsed/refractory chronic lymphocytic leukemia (CLL). We – along with clinicians – are very excited about both of these trials.
ALPHA3 will evaluate cema-cel as part of a 1L consolidation regimen in LBCL patients who are most likely to relapse. This is an incredibly innovative trial and one that just wasn’t clinically possible until now.
The desired outcome of this pivotal trial is for cema-cel to be embedded in the 1L setting to potentially boost cure rates, rendering later-line treatment obsolete and making cema-cel available in community cancer centers where most earlier line patients seek care. Another key product candidate in development targets renal cell carcinomas using a CD70-targeted CAR T, a promising approach for the most common form of kidney cancer. This solid tumor program has shown potential in Phase I trials, with ongoing enrollment indicating the breadth of our efforts to combat various cancers with our innovative allogeneic CAR T-cell products.
Your technology also targets autoimmune diseases. Can you discuss your recent collaboration with Arbor Biotechnologies and the potential of CAR T products for treating autoimmunity?
Indeed, we believe our technology's application extends beyond oncology to treating treatment-resistant autoimmune disorders, such as lupus and lupus nephritis, with increasing clinical proof of concept in various disorders. The field's approach of repurposing cancer CAR T-cells for autoimmune diseases seemed inadequate to us, prompting a tailored strategy. In 2023, we initiated a project to design a product specifically for autoimmune patients, leading to the development of ALLO-329. This unique product candidate, featuring both CD19 and CD70 CARs, targets both B and T cells, offering a novel approach to treating autoimmune diseases by potentially resetting the immune system with reduced or no chemotherapy preconditioning.
The collaboration with Arbor Biotechnologies provides us access to Arbor’s CRISPR-based gene editing platform, differing from the TALEN® technology used in our oncology programs. This strategic move underlines our commitment to advancing the treatment of autoimmune diseases by developing potentially groundbreaking CAR T-cell products that have the added benefit of scale to meet the demands of this market.
You recently ceased enrollment in two advanced lymphoma trials, deeming them obsolete. Why?
Our decision to deprioritize enrollment in these trials, targeting relapsed refractory LBCL, stemmed from a strategic reassessment. The patient demographic for these trials mirrored that of earlier studies, but with evolving treatment modalities and diminishing unmet needs in third-line settings, it became evident that these trials no longer aligned with our mission or market opportunities. Our focus on the ALPHA3 trial, which we are very excited about, would also serve to potentially accelerate obsolescence in later lines. This pivot reflects our adaptive strategy to ensure our research efforts and resources are directed towards areas with the highest impact and market viability.
In terms of economics, are you optimistic about the future, especially given the recent upward trend in Allogene Therapeutics' stock?
While predicting the stock market's future is challenging, the positive response from investors, analysts, and partners to our strategic decisions and plans signals a renewed interest in Allogene's scientific leadership. The enthusiasm surrounding our announcements, including the shift to the ALPHA3 trial and our foray into autoimmune disease, suggests a promising outlook. Our hope is that as we continue to execute on our trials and new opportunities, this momentum will not only sustain but also grow, reflecting our commitment to innovation in cell therapy and biotechnology.
Looking ahead, where do you see Allogene Therapeutics in five years?
We are taking an entirely new approach to development and clinical trial design that I believe creates an advantage for our investigational products. In five years, I see Allogene Therapeutics having secured FDA approval for several of our products in both oncology and autoimmune disease treatment realms. The current slate of initiatives underscores our position at the forefront of cell therapy and biotech innovation and our drive to make CAR T accessible for all eligible patients. Success in any of these endeavors could transform the lives of thousands, potentially tens of thousands, by offering new, lifesaving treatments. As we discuss our progress in the future, I anticipate not only celebrating these achievements but also looking forward to the next wave of scientific breakthroughs and treatments that continue to improve patient outcomes.
