American Society for Hematology (ASH) 2019 Annual Meeting: Our Recommended CAR T Cell Therapy Innovation Talks

The American Society of Hematology’s (ASH) annual meeting is a well-established indicator of the innovations that are coming down the pipeline for hematologic diseases. As this year’s meeting approaches (Dec 7-10), CBPartners’ experts from our Cell and Gene Therapy Center of Excellence have selected 8 promising presentations on the future of CAR T cell therapy to attend. CAR T landscape is rapidly evolving with immense future potential, and the team are excited to share their favorite picks.

For further information on CAR Ts and other cell and gene therapies, read: CAR T – Cell therapies: How close are we to meeting the remaining needs of patients? or CAR T Combos: Potentially the next big thing in solid tumors, yes pricing ‘sticker shock’ is not the only hurdle to overcome

1. EDITING T CELLS FOR BETTER EFFICACY

Saturday, December 7, 2019: 7:30 AM
W414AB, Level 4 (Orange County Convention Center)

Title: First-in-Human Assessment of Feasibility and Safety of Multiplexed Genetic Engineering of Autologous T Cells Expressing NY-ESO -1 TCR and CRISPR/Cas9 Gene Edited to Eliminate Endogenous TCR and PD-1 (NYCE T cells) in Advanced Multiple Myeloma (MM) and Sarcoma

https://ash.confex.com/ash/2019/webprogram/Paper122374.html

CBP Summary: An exciting study where T cells were genetically modified to remove the endogenous TCR, enhancing expression of the targeting molecule and thus potentially improving their ability to eliminate tumor cells. Expression of the endogenous PD-1 gene was also eliminated to stop any immune checkpoint-related silencing. It is a very early study of N=3 patients, but the lack of severe AEs so far is encouraging. Similar approaches modulating activation and silencing pathways of the immune system might finally help cell therapies achieve success in solid tumors.

2. ACHIEVING DURABLE CLINICAL RESPONSES

Saturday, December 7, 2019: 8:00 AM
W414AB, Level 4 (Orange County Convention Center)


Title:
Third-Generation CAR T Cells Targeting CD19 Are Associated with an Excellent Safety Profile and Might Improve Persistence of CAR T Cells in Treated Patients

https://ash.confex.com/ash/2019/webprogram/Paper125423.html

CBP Summary: Commercially available second-generation CAR Ts use one of two co-stimulatory domains; CD28 or 4-1BB. The CD28 domain is considered to drive rapid amplification of the T cells resulting in quick elimination of the tumor, while 4-1BB is thought to provide long-term persistence after a slower ramp up. Third-generation CAR constructs aim to provide the best of both worlds by including the two co-activation domains in tandem, potentially improving safety, efficacy, and durability. This presentation will report results from an early stage trial.

3. THE IMPACT OF MICROENVIRONMENT ON NOVEL IMMUNOTHERAPEUTIC APPROACHES

Saturday, December 7, 2019: 10:30 AM
Valencia A (W415A), Level 4 (Orange County Convention Center)

Title: The Impact and Modulation of Microenvironment-Induced Immune Resistance Against CAR T Cell and Antibody Treatments in Multiple Myeloma

https://ash.confex.com/ash/2019/webprogram/Paper125818.html

CBP Summary: A reminder to not forget about the cells surrounding the tumor (i.e., the microenvironment), which might impact the ability of any cell therapies to attack. This study from researchers in the Netherlands evaluates how bone marrow cells are impacting the efficacy of CAR Ts in targeting MM cells. The suggested next step from these researchers is to infuse CAR Ts alongside agents that can remove the tumor defenses against the CAR T cells.

4. NEW TARGETS FOR CAR T CELL THERAPY

Saturday, December 7, 2019: 12:00 PM
Valencia A (W415A), Level 4 (Orange County Convention Center)

Title: Safety and Anti-Tumor Activity of CD5 CAR T-Cells in Patients with Relapsed/Refractory T-Cell Malignancies

https://ash.confex.com/ash/2019/webprogram/Paper129559.html

CBP Summary: So far, a lot of the targeted cell therapy efforts have been focusing on two markers of the tumor cells: CD19 for NHL and B-ALL and BCMA for MM. An increasing number of proteins are expected to be in coming years and this presentation will share encouraging response rates in heavily pre-treated patients with T-cell malignancies (T-ALL, T-NHL), from a small study (N=9) with CAR Ts targeting a new surface molecule, CD5.

5. OPTIMISING MANUFACTURING TECHNOLOGY FOR A BETTER CELL THERAPY

Saturday, December 7, 2019: 12:15 PM
Valencia A (W415A), Level 4 (Orange County Convention Center)

Title: Donor-Derived CD19 CAR Cytokine Induced Killer (CIK) Cells Engineered with Sleeping Beauty Transposon for Relapsed B-Cell Acute Lymphoblastic Leukemia (B-ALL)

https://ash.confex.com/ash/2019/webprogram/Paper125894.html

CBP Summary: There are a few different innovations highlighted in this presentation on the outcomes of a small study from an Italian group: 1) A specific subset of T-cells (cytokine-induced killer cells) were used to produce the CAR T product; 2) Cells were taken from donors, i.e., an allogeneic source; 3) The cells were modified with a non-viral vector, which should be easier to produce (Sleeping Beauty transposon). In the future, all three methods, currently advanced by other groups as well, can support manufacturing of better-defined cell therapies at a faster and less resource-intensive manner.

6. EXTENDING DURABILITY TO AVOID RELAPSE

Saturday, December 7, 2019: 2:00 PM
Tangerine 3 (WF3-4), Level 2 (Orange County Convention Center)

Title: Novel CD19t T-Antigen Presenting Cells Expand CD19 CAR T Cells In Vivo

https://ash.confex.com/ash/2019/webprogram/Paper131346.html

CBP Summary: While CAR Ts promise durable efficacy as a “living therapy,” persistence over several years is not yet guaranteed, which might result in disease relapse once the CAR T cells are gone from the bloodstream. This human study tested the concept of boosting CAR T cell volume in patients, aiming to increase their persistence through the periodic infusion of antigen presenting cells (APCs). While results are not yet conclusive, it is certainly an interesting approach to resolve a common issue associated with the technology.

7. UNDERSTANDING IDENTIFIERS OF CAR T RESPONSE

Monday, December 9, 2019: 11:15 AM
W414AB, Level 4 (Orange County Convention Center)

Title: Identification and Validation of Predictive Biomarkers to CD19- and BCMA-Specific CAR T-Cell Responses in CAR T-Cell Precursors

https://ash.confex.com/ash/2019/webprogram/Paper122513.html

CBP Summary: CAR Ts produced from a given patient’s blood consist of a complex mix of different types of T cells, each with different functions and features – this study aims to advance our understanding of which cell mixes might correlate with response in different disease areas. Gaining a clearer picture of how T cells attack and eliminate tumors can allow for fine tuning of CAR T manufacturing, achieving more consistent and potentially more effective final products.

8. TARGETING TWO SURFACE MOLECULES TO DECREASE THE RISK OF RELAPSE

Monday, December 9, 2019: 4:00 PM
W224CDGH, Level 2 (Orange County Convention Center)

Title: Phase I Trial Using CD19/CD22 Bispecific CAR T Cells in Pediatric and Adult Acute Lymphoblastic Leukemia (ALL)

https://ash.confex.com/ash/2019/webprogram/Paper129411.html

CBP Summary: A common mechanism for relapse after CAR T therapy is loss of the target antigen (e.g., CD19, BCMA) rendering CAR T cells incapable of recognizing the tumor cells, even if they persist in the bloodstream. One potential method of getting around this limitation is to target two antigens at once (e.g., CD19 and CD22 for ALL). There are a number of trial analyses testing this hypothesis in ALL and MM, but we have selected this particular abstract submitted by researchers across the USA, due to the inclusion of a challenging population, including post-BLINCYTO, post-CAR T, and post-BESPONSA patients.

CBPartners Cell and Gene Therapy Center of Excellence (CoE) focuses on assessing the unique opportunities and challenges associated with the emerging class of novel treatments. With a lens towards identifying key value, access, and pricing dynamics, our team can determine the influence these innovative treatments will have when entering the market.

If you’re interested in finding out more about CBPartners’ work in this landscape, please contact Julia Pikus, Associate Principal and co-founder of the Cell and Gene Therapy CoE Julia.pikus@cbpartners.com

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