Allogene takes the stage in New York to go deep on its off-the-shelf cell therapies — declaring a first for solid tumors

NEW YORK — In most cases, a biotech like Allogene would wait until the next big science conference to offer its latest series of snapshots of its data. But most biotechs aren’t like Allogene, where the veteran leaders from Kite garnered a substantial number of kudos over the years for their in-depth reviews of the company’s progress.

Bioregnum Opinion Column by John Carroll

So on Tuesday, the leaders at Allogene converged on Manhattan once again to give a detailed breakdown of their latest steps forward, looking to stay out front in the busy off-the-shelf cell therapy arena, keep a clean bill of health on the safety front and prove that they can not only match the autologous pioneers they helped create but make the all-important leap into solid tumors. It’s another step forward in a journey that has a long way to go before even the first big regulatory finish lines appear on the track. But for CEO David Chang, who spent some time with me running through the data ahead of the Tuesday session, it all amounts to forward momentum toward the desired goal.

Top of the list of salient points to make today: Chang staked a claim for the first early data catch demonstrating a positive impact on solid tumors for an off-the-shelf cell therapy.

Says Chang:

I think this is the one that I am most excited about, which is what we are showing in the solid tumor with ALLO-316. This is a CD70 targeted tumor. We have treated a number of patients, 17 altogether.

Initially, we did not necessarily require patient tumors to be CD70 positive, but we looked at the tumors when they are available for CD70 status after they were involved and treated. So when you do that, out of 17 patients, we have nine patients who are known to express CD70 in their tumor. The other eight patients are either CD70 negative or status unknown. So the most relevant patient population is that nine patients. And we are seeing three responses out of nine patients. So think about this: These are kidney cancer patients after they’ve been treated with the immune checkpoint inhibitor, as well as a VEGF-targeted therapy. These patients really don’t have any actions. And even in that kind of patient population, CAR-T therapy can provide efficacy that we are showing in the Phase I study. Then we are still optimizing the cell dose as the study progresses. But the early data provides very convincing and I would almost say compelling evidence of anti-tumor activity of ALLO-316 in solid tumors.

If you think about what we’ve been doing over the last few years, it’s really trying to ground ourselves in hematologic cancer and also at the same time trying to move into the solid tumor. And this is the first time that we are showing that our solid tumor approach with an allogeneic CAR-T is beginning to show clinical activity.

There’s a lot more to the presentation — which is packed with data points on the lead therapies. Allogene obviously has a huge distance to go in solid tumors, proving that the first responses are real and durable and relatively safe. This is something Chang understands all too well, after leading the development of Kite’s CAR-T Yescarta. Off-the-shelf data in hematology have to stand up against the autologous set so that it can prove more practical and remain just as effective. And it’s playing out while rivals in the field gun for better data and the groundbreakers at Kite/Gilead and Novartis work on the manufacturing obstacles that have prevented treatment in some cases.

Along the way, they’re working on dosing and manufacturing, offering a blizzard of data points in a whole range of subgroups.

It’s immensely risky, as Allogene demonstrated during an FDA hold on a safety scare that delayed the work while they sought to prove to regulators that their approach included manageable safety issues. Now they have data from 175 patients in the CD19 program, which they see as solid evidence of a model picture of durability and efficacy.

Last year, Chang says, they reported 14 complete responses in the CD19 program, where the overall response rate has run at 67% with CRs at 57%. A year ago, 10 of them were still alive, and now, 12 months later, nine of them are alive.

Here’s Chang again:

So put it this way, over a one-year period, we only lost one response which happens, which is something that we have seen in autologous cells in a setting. And we have nine patients who are in a complete remission for 12 months or longer. So to me, that is one really compelling bit of evidence that this field has been looking for.

Allogene only recently began its pivotal study, a Phase II trial of ALLO-501A for LBCL, that will put all this to the bigger test required by the FDA and the EMA for an approval. And they don’t expect to start reporting the all-important data from that until the first half of 2024. But if you’re into painstaking detail on the data, and care a lot about cell therapy, the presentation they’re making today offers another clear picture of incremental, but significant, progress.

ASH, Chang says, would not have offered a stage for everything they want to talk about today. So they’re coming to Manhattan to make their case in the face of a frigid market reaction to most things biotech this year.

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