CAR T Sector Update

The CAR T sector has been under the regulatory microscope since the FDA announced in late November 2023 that it was investigating 20 reports of T cell lymphoma in patients who had previously received CAR-T therapies. However, at least one cell therapy oncology company is not concerned.

At the 42nd J.P. Morgan Healthcare Conference, Triumvira Immunologics President and Chief Operating Officer Rob Williamson told BioSpace that internal discussions and those with other analysts and oncology-based cell therapy companies indicate the investigation is not a “big deal.” He was also adamant that it would not affect Triumvira and its business.

“(For) these patients, the risk-benefit is significantly in favor of the therapy,” Williamson said.

That is not to say that the CAR T industry has not had some rough times recently or that everything is sailing along smoothly.

“I think cell therapy within biotech is still in the penalty box,” Williamson said. He said cell therapy companies may continue to be seen less favorably than other biotechs during the next year, except for those who can differentiate themselves in showing value, good efficacy data or by targeting unmet needs. He said he is hopeful that cell therapy can get out of this penalty box, “but it’s a very crowded space.”

Upcoming Events

Austin, TX, Hamilton, ON and South San Francisco, CA – Dec. 19, 2023 /PRNewswire/ — Triumvira Immunologics, a clinical-stage company developing novel, targeted autologous and allogeneic T cell therapeutics, today announced that it will present two abstracts at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in San Francisco, California, from January 18-20, 2024. The company will showcase clinical data from its ongoing Phase I/II studies investigating the safety and efficacy of autologous TAC-T cells targeting human epidermal growth factor receptor 2 (HER2) and Claudin 18.2 (CLDN 18.2), respectively, in relapsed or refractory solid tumors (TACTIC-2 /NCT04727151, TACTIC-3 /NCT05862324).

The technology behind TAC01-HER2 and TAC01-CLDN18.2 stands as an innovative cell-based therapeutic modality, harnessing genetically engineered T cells derived autologously. These T cells are equipped with a T-cell Antigen Coupler (TAC) rationally designed to specifically recognize HER2 or CLDN18.2 within tumor cells.

Phase 0 Imaging Studies

First-in-human phase 0 imaging studies are also known as microdosing proof-of-concept studies and are designed to speed up the development of promising drugs or imaging agents by establishing very early on whether the drug or agent behaves in human subjects as was expected from preclinical studies. Distinctive features of phase 0 studies include the administration of single subtherapeutic doses of the study drug to a typically small number of subjects to gather preliminary human in vivo data on pharmacokinetics, pharmacodynamics, and the target. They enable go/no-go decisions to be based on relevant human models instead of relying on animal data, which can be unpredictable and vary between species. A phase 0 study gives no data on safety or efficacy to cause any therapeutic effect and less risk to human toxicity.

The recent advancements and the great potential of Theranostics technology has allowed the utilization of radioimmune conjugates for diagnosis and treating various diseases in humans. To this end, the use of radiopharmaceutical drugs in phase 0 human studies and prior to early-phase human clinical trials are poised to become more mainstream and strategic regulatory guidance toward rapid, safer, cheaper, and more informed developmental decisions in 2024 and beyond. GBI Biomanufacturing is a U.S.-based CDMO with about 20 years of experience and expertise in the radioimmune conjugate (and bioconjugation) arena.

CAR T-Cell Therapies

By no means should cyborgs be disparaged—even if they are very small. The U.S. Food and Drug Administration (FDA) has approved multiple cellular cyborgs—more commonly known as chimeric antigen receptor (CAR) T-cell therapies—for various blood cancers since 2017.

In these therapies, the patient’s own T cells are collected and genetically engineered so that they produce an artificial protein—the CAR—that will target specific antigens found on cancer cells. Once the cells are engineered, they are infused back into the patient. Unlike the all-but-unstoppable cyborgs of science fiction, CAR T cells are stoppable. For example, they have struggled against solid tumors. Consequently, some therapeutic developers have been exploring alternatives to CAR T cells. One such company is Alloplex Biotherapeutics.

Predictions for 2024

This year’s predictions on the biopharma financing and funding environment are more optimistic than they were last year, with the persistent caveat of macroeconomic uncertainty, plus unresolved litigation on policy issues. With deal activity increasing and the promise of novel product approvals in key therapeutic areas next year, small biotechs and some Big Pharmas appear poised to steer the industry into calmer waters. Business model creativity will become increasingly mandatory for companies marketing expensive products for small patient populations and larger population drugs in categories like obesity and CNS disorders.

ABSTRACT

Background

The T cell antigen coupler (TAC) is a novel, proprietary chimeric receptor that facilitates the redirection of T cells to tumor cells and activates T cells by co-opting the endogenous T cell receptor complex with the goal to elicit safe and durable anti-tumor responses.

Materials and Methods

The potency and safety of HER2-TAC γδ T cells generated from multiple donors was evaluated using a variety of in vitro and in vivo assays, including flow cytometric analysis, cytotoxicity assays, and mixed lymphocyte reactions (MLR).

Results

HER2-TAC γδ T cells selectively reacted to HER2-expressing tumor cells in vitro, showing strong anti-tumor efficacy in HER2-positive tumor xenograft models without signs of toxicity.

Conclusions

HER2-targeted TAC γδ T cells display strong and specific activity against HER2-expressing tumor models, highlighting the versatility of the TAC platform for therapeutic applications in solid tumors.

ABSTRACT

Background

The TAC receptor activates T cells by co-opting the endogenous T cell receptor machinery and has been shown to retain cytotoxicity capacity during and after repeated tumor challenges in vitro and in vivo.

Results

Evidence indicates that TAC-T cells controlled tumor cell growth through multiple rounds of tumor cell challenge and demonstrated long-term ex vivo proliferative and cytotoxic capabilities, suggesting long-lasting T cell persistence against solid tumors.