Revolutionizing Treatment in the Battle Against Blood Cancer

Last September, on my first day at Allogene, I had the privilege of attending an internal Blood Cancer Awareness Month event, which has set the tone for each day since and remains one of my favorite memories at the company thus far. I witnessed Allogene’s culture of comradery and passion; the genuine motivation and desire to achieve something transformational in cancer by investigating genetic engineering of T cells from healthy donors, and to make a difference in the lives of blood cancer patients. Regardless of the month, our team shows up focused and dedicated to that mission. I could not be prouder to be part of it. Collectively, we share a devotion to discovering the next revolution in cancer treatment, and at Allogene, delivering a potential new treatment for different blood cancers is where we have decided to start.

Currently, there are about 1.3 million people living in the U.S. alone who have been affected by blood cancer.¹ In 2020, approximately 180,000 more people will be diagnosed.¹ While decades of research and clinical trials have brought us practice-changing treatment options resulting in a 50% increase in the five-year survival rate for myeloma and 35% increases for leukemia and non-Hodgkin lymphoma (NHL), most blood cancer five-year survival rates are still far lower than many other cancers² and some represent among the most difficult to treat of all malignancies.

The truth is that the latest innovations in blood cancer treatment, autologous CAR T therapies and bi-specifics, fall short for many patients. Autologous therapy is a significant life-saving advancement in current cancer treatment, but it’s not without its challenges: leukapheresis, lengthy vein-to-vein times, potential need for multiple infusions, variable potency, high production costs and manufacturing shortfalls. While these therapies are meaningful and important, what can we do to make such life-saving therapies more accessible to everyone?

Allogene has a vision for a solution: allogeneic (AlloCAR T™) therapy. Our investigational approach aims to mitigate four key challenges presented by autologous CAR T therapy – access, cost, speed and reliability. Using T cells from healthy donors instead of patients themselves, as is the case with autologous CAR T therapy, we believe we have the potential to address each of these challenges and more.

At scale, a single manufacturing run of AlloCAR T therapy has the potential to treat over 100 patients, reducing overall costs of treatment and creating a stock of treatment. This eliminates the need for lengthy and complex manufacturing and preparation logistics and enables repeat dosing for patients. The ability to stock treatment opens the door for on-demand therapy for patients who are critically ill and do not have the time to wait for the preparation required for traditional autologous CAR T therapies, or who lack enough T cells for harvesting and expansion. By initiating the CAR T development process with healthy T cells, there is also potentially less variability.

With our AlloCAR T platform, patients will not need to undergo leukapheresis (a laboratory procedure in which a patient’s white blood cells are separated, and the remaining blood cells and plasma are returned to the patient). We engineer our T cells to express CARs, which are designed to recognize certain cell-surface proteins expressed in hematologic or solid tumors and use gene editing to reduce the risk of graft-vs-host disease (GVHD) and allogeneic rejection.

In my one year at Allogene, we have already made progress towards our goal of revolutionizing cancer treatment for patients. Recently, we presented initial data from our Phase 1 ALPHA trial at the virtual American Society of Clinical Oncology (ASCO) meeting, for our ALLO-501 therapy in combination with ALLO-647, our proprietary anti-CD52 monoclonal antibody (mAb)-based lymphodepletion regimen in patients with relapsed or refractory NHL. While we are excited by the promising initial findings, these findings will need to be confirmed with more patient experience and longer follow-up times.

Cancer research is iterative work, but occasional exponential innovations can make a life-changing difference for a broad spectrum of patients. This is where real revolutions in treatment begin. It is this understanding that fuels our work at Allogene, as we seek to create our AlloCAR T platform for tomorrow. One example of our vision to innovate on our core AlloCAR T platform is to utilize gene editing to create next generation technologies. We are doing this with our internally developed TurboCAR™ technology. TurboCARs are designed to engineer cytokine signaling selectively into the CAR T cells to potentially “turbocharge” the potency and durability of these engineered cells, while mitigating systemic toxicity. We are excited about what this technology may mean for future AlloCAR T therapies and as we look to develop our first TurboCAR candidate, ALLO-605, for patients with relapsed or refractory multiple myeloma.

At Allogene, we are not just looking to deliver an allogeneic CAR T therapy – we are striving to build an industry-leading platform. Beyond TurboCARs, we are progressing other optimized methods by leveraging both our existing partnerships and own internal capabilities. Under our partnership with SpringWorks Therapeutics, we plan to evaluate ALLO-715 with their investigational gamma secretase inhibitor (GSI), nirogacestat, in patients with relapsed or refractory multiple myeloma. Data presented by other companies at the American Society of Hematology Annual Meeting in December 2019 suggest that a GSI could make BCMA a more apparent target by increasing expression in multiple myeloma cell lines, and therefore has the potential to make our AlloCAR T therapy more efficacious. Another area of intense interest is iPSCs – or Induced Pluripotent Stem Cells – which are cells that can be engineered at the stem cell stage and could allow us to one day create a clonal cell bank, potentially granting us a limitless supply of starting material for our therapies. Our exclusive license agreement with Notch Therapeutics allows us to utilize their proprietary bead-based platform to develop iPSC AlloCAR T products for initial application in non-Hodgkin lymphoma, leukemia and multiple myeloma. The next frontier is solid tumors. We plan to embark on that journey starting in renal cell carcinoma for our anti-CD70 investigational therapy, ALLO-316.

In drug development, the path is never easy but our ingenuity has the potential to give patients with cancer time. Time with family. Time with friends. Time to make a difference. And this has been our greatest motivation in R&D. We believe we are progressing our goal to make AlloCAR T therapy the next great breakthrough in cancer treatment. I look forward to another year in this relentless pursuit to defeat blood cancers and a future time in which September is simply but another month on the calendar. 

References

1 https://www.lls.org/facts-and-statistics/facts-and-statistics-overview/facts-and-statistics

2 https://www.llscanada.org/disease-information/facts-and-statistics#:~:text=Survival,to%2085%25%20for%20Hodgkin%20Lymphoma.