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Five years ago, the FDA approval of autologous CAR T therapy for the treatment of certain late-stage blood cancers started a revolution. This was a major step forward in cancer treatment and life changing for many patients who were running out of options.

While leading research and development at Kite Pharma, I was fortunate to play a role in the development of the first autologous CAR T for non-Hodgkin lymphoma (NHL), culminating ultimately in a ground-breaking approval that radically changed how aggressive NHL is treated today. Yet even as our excitement grew about the curative potential of autologous CAR T, we knew its bespoke manufacturing process and complex supply chain would limit the number of patients who would benefit. Today many — the number likely to be in the thousands — patients in need of autologous CAR T therapy are deteriorating on waiting lists as their disease worsens.

We need another revolution. One that shifts CAR T from a complex, individualized therapy to an off-the-shelf product that can be delivered on demand, reliably and at scale — bringing new hope to patients enduring agonizing waitlists, and the physicians who treat them.

Patients who can benefit from this game-changing treatment need an option that does not require the slow and complex individual manufacturing runs required for autologous CAR T. Dr. Arie Belldegrun and I foresaw this need years ago, and that’s the reason we launched Allogene in 2018, bringing together a dedicated team and working together with clinical trial investigators, regulators and most importantly patients, to help break the predicted access bottleneck that we have now.

We are making progress. Allogene recently presented data showing that, for the first time, an investigational allogeneic CAR T product for relapsed/refractory large B-cell lymphoma (LBCL) could be safe and effective, and importantly, produce deep and durable responses similar to approved autologous CAR T therapies.[1]

Why we need allogeneic: the waiting game is hurting patients

As anyone can imagine, for seriously ill patients and their loved ones, the bottleneck to access treatment is beyond stressful. Even as ground-breaking as autologous CAR T has been, it requires patients to wait ­— wait for harvesting of cells, wait to see if their cells can be individually manufactured, and finally, wait for their cells to be returned to the clinic and reinfused. This complex and lengthy process, from the initial decision to undergo CAR T therapy to finally receiving the CAR T, can take anywhere from three weeks to more than six months.

In a recent Allogene-sponsored survey of 50 U.S.-based hematologist-oncologists, physician assistants, nurse practitioners, and registered nurses from academic centers with CAR T therapy capabilities, 82% of respondents agreed that CAR T therapies have changed how they manage aggressive cancers, but extensive wait times and manufacturing limitations keep many eligible patients from receiving treatment.[2]

Of patients eligible for treatment, only 12% are able to receive treatment within one month, with approximately 40% waiting three to six months or longer to receive treatment.2

We are making progress advancing the science of CAR T to meet these needs

Unlike autologous CAR T, allogeneic CAR T investigational products utilize cells from healthy donors, making them “off-the-shelf” in nature and able to be efficiently manufactured in large batches and kept stored for on-demand delivery to patients.

Our allogeneic CAR T products have the potential to treat approximately 100 patients with a single manufacturing run, creating the possibility of treating 20,000 patients annually from one manufacturing facility. That kind of scale is not possible with autologous CAR T, which would require one manufacturing run to treat one patient – thousands of manufacturing runs if thousands of patients were to be treated. In comparison to the lengthy and complex procedure associated with autologous CAR T that keeps patients in waiting from weeks to months, an off-the-shelf allogeneic product can be administered within days.

We are still in the early days of realizing the potential of allogeneic CAR T. It is unlike anything before it, and now we must prove that this new modality can be safe, effective and, importantly, durable. Patients and clinicians know that even with the bottleneck problems, the effectiveness of autologous CAR T has been revolutionary, so the bar is high.

And we are taking steps to make that happen. In total, we now have data from over 175 patients across our allogeneic pipeline, the most ever in the allogeneic CAR T field. In October, we announced the initiation of the industry’s first potentially pivotal Phase 2 clinical trial for patients with relapsed/refractory LBCL. We also recently released data from our trials in this form of NHL showing an allogeneic CAR T product can be safe and effective, with durability of remission, on par with today’s FDA approved autologous therapies. This exciting new durability data checks an important box that supports us continuing the Phase 2 trial that is intended to demonstrate the true promise of allogeneic CAR T.

Our lead program for patients with relapsed/refractory LBCL showed deep and durable responses in Phase 1 trials. As shown at our R&D Showcase, nine of the 10 patients who were in complete response, or remission, one year ago remained in complete response, now all beyond 12 months. In two patients durable complete response was ongoing more than two years, and a third patient was approaching the two-year evaluation.

In our Phase 1 trial in multiple myeloma — where the patient need is acute — we’ve shown encouraging responses, and we are now working on optimizing our manufacturing and starting to plan for a potentially pivotal Phase 2 trial for this program.

The next breakthrough in CAR T is in treating solid tumors. We’ve shared initial promising data at our R&D Showcase that showed clear activity in patients with advanced or metastatic clear cell renal cell carcinoma (RCC). Findings showed that in patients with RCC who expressed a biomarker called CD70, a one-time infusion of an allogeneic CAR T product candidate resulted in a 100% disease control rate. Of those, 33% experienced a partial response or greater than 30% reduction in the size of tumors. This data is exciting because it is the first time that clear activity against solid tumors has been shown for allogeneic CAR T, and we are excited to continue our Phase 1 trial to explore safety and efficacy of our product candidate.

I believe we are entering a new era in the development of our AlloCAR T™ investigational products, one in which the field can soon start to turn its attention to “when” and not “if” allogeneic CAR T can begin to break this bottleneck and provide great benefit to patients with certain cancers.

Doing more: new effort to advance science, expedite allogeneic clinical trials

Making CAR T therapy scalable would make it more accessible to patients with certain cancers, and that’s the driving force behind CAR T Together, a new coalition of leading clinical trial investigators representing the field of clinicians who are committed to supporting the development of off-the-shelf CAR T products.

CAR T Together will support expediting the clinical trial work so that allogeneic CAR T can reach its true potential and break that bottleneck that is keeping patients from getting the treatment they need.

Our collective focus is to advance the science toward making effective treatments available on a wide-scale basis. We believe this is the promise of allogeneic CAR T products, meeting that major unmet patient need.

The ultimate goal: advancing an option that can treat more people with cancer faster, more reliably and at greater scale. Because no patient should have to wait, and no physician should need to decide who gets the therapy that may offer a chance at life.

References

[1] Allogene, R&D Showcase, November 29, 2022
[2] Allogene data on file.