New Precision Platform Could Be Cell Therapy Game-Changer – BioSpace

BlueSphere CEODr. David Apelian, M.D., Ph.D/Courtesy BlueSphere Bio

One of the greatest recent innovations in cancer treatment, CAR T therapies have sent some patients into long-lasting remission, with speedier recoveries, due to the lack of aggressive chemotherapy involved. They are the darling of numerous biopharma companies,including Sorrento Therapeutics, Kite Pharma (Gilead), and Allogene Therapeutics.

But they still have their limitations. They can only target a single tumor-associated antigen, recognize only cell surface antigens, and are not wholly tumor-specific, only targeting proteins expressed by normal and malignant cells. Enter BlueSphere Bio, a small biotech aiming to overcome these challenges with a precision approach to T cell therapy.

Headquartered in Pittsburgh, Pa.,and founded in 2018, BlueSphere has been operating under the radar. Not anymore. BioSpace sat down with Chief Executive Officer Dr. David Apelian, M.D., Ph.D., who shared why he believes the companys TCXpressis the premier T cell receptor platform that can have a significant impact on cancer.

When Apelian spoke with Co-Founder and Chief Scientific Officer Dr. Mark Shlomchik, M.D., Ph.D., about technologyhe was developing that could rapidly screen and capture thousands of T cell receptors from the sample more efficiently and cost-effectively than traditional methods, he was intrigued.

If you could identify those receptors that will direct the T cells to kill a tumor, amplify those cells in greater number outside the patient in a test tube, so to speak, and then reintroduce a healthy version of that T cell into the patient, youve essentially transcended what vaccines are hoping to do, said Apelian, who was previously chief medical officer at GlobeImmune, one of the early leaders in cancer vaccines. Youre getting right to the endpoint that you want.

The overall approach also consists of a downstream program that utilizes BlueSpheres NEOXpressplatform, which will enable the individualization of treatments for specific cell tumors.

BlueSphere profiles tumor cells by DNA and RNA sequencing and identifies the neoantigen profile in those tumors. In parallel, were extracting the T cells from that same tumor, were identifying the repertoire of TCRs, and then were marrying the two datasets up. Its a multiplex approach, Apelian said. Next, they will identify the ones that light up,characterize those T cell receptors and their ability to kill the tumor, and specifically recognize the target antigenbut not the native antigen.

BlueSphere will put the platform to its first test late in 2022 with the planned launch of a clinical trial in bone marrow recipients with high-risk leukemia. Apelian shared that acute myeloid leukemia (ALL) is likely to be the lead indication in that program. Here, they will be targeting minor histocompatibility antigens.

When a high-risk AML patient has not responded to first-line therapy or failed a first bone marrow transplant, Apelian said the chance of a successful transplant is probably 10%if that. While essentially a match, there are still many minor variations between a donor and recipient. This program aims to raise those odds.

We can engineer a T cell into the donor cell, which the recipient is already getting anyway; we can eliminate all the other minor antigen variants, and then shift that to a leukemia-only response, he explained. This enables complete engraftment, knocking out any residual leukemia cells along with the patients marrowand ultimately leading to improved long-term survival.

This is an example of an allogeneic, off-the-shelf target. On the other end of the spectrum, BlueSpheres technology enables it to take a preciseapproach to each patients tumor.

Apelian explained that certain cancers called hot tumorspossess a high number of different antigens. Melanoma probably has the most complex neoantigen profilebecause these tumors are caused by exposure to the sun, which allows more mutations to occur. Non-small-cell lung cancers also have a fair number of neoantigens.

We can literally take a patients tumor and extract the tumor-specific antigens that patient has generated uniquely in their own tumor, and then identify the receptors to target the patients very own tumors, Apelian said.

The benefit of this individualized therapy, he continued, is that the patients body is already making those T cell receptors, so its very unlikely were going to make a receptor thats going to be toxic to the patient.

Then, BlueSphere can enrich these receptors, grow them in large quantities in a re-engineered healthy version of the T cell, and replace them in the patients body.

Those T cells are sick;theyre exhausted. So, were taking that receptor part and re-engineering it into a healthy version of their own T cell, and then reintroducing it into the patient, Apelian said. Thats going to be the game-changer for solid tumors.

Conversely, there are other cancers known as cold tumors. These include ovarian cancer, prostate cancer, pancreatic cancer, glioblastomas, and most breast cancers. Apelian believes his companys platform has the throughput capability to tackle these as well.

We think we have enough throughput with our TCXpressto even identify TCRs for those neoantigens in so-called cold tumors, but thats kind of a downstream project for us, he said.

In the middle of this range, BlueSphere will look at other exciting targets for solid tumors that can be re-engineered ahead of time to treat a myriad of different cancers.

While some elements of the work will be off-the-shelf, and there is a movement in the industry toward finding a universal cell, Apelian explainedmany advantages to the autologous approach.

I understand the motivation for that [quest for a universal cell], but I think youre going to lose a lot of the specificity and the elegancethe exquisite specificity of T cell, he said. We think its going to be more likely that autologous approaches and individualized therapies will be safer and more effective.

BlueSphere is conducting what it calls the virtual patient program to determine the next steps in its pipeline. Instead of waiting to completemanufacturing aspects necessary for individualized tumor therapies, the company is building a tissue repository to test various tumors. Here, they will identify the neoantigen profile, extract the T cell repertoire from the tumor, and characterize the potential to recognize and kill the tumor.

Were collecting tissues, local tissues and some tissues from the National Cancer Institute, and were testing as if they were patients in a study, Apelian explained.

He also expressed an interest in working collaboratively to solve cancers outside of BlueSpheres purview and other diseases. I could see this [technology] being useful a huge array of diseases that we can treat by appropriately re-engineering T cells to have the right T cell receptors, he said.

With obvious ambition and belief in its platform, BlueSphere expects to double its workforce, which sits at 38 people, over the next 18 to 24 months.

Its a super exciting time for the company, Apelian said, It feels like moonshot startup excitement, which is fun. Everyone kind of appreciates how game-changing this platform could be.

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New Precision Platform Could Be Cell Therapy Game-Changer - BioSpace