With so much investor interest surrounding the potential of allogeneic CAR T cell therapies, the stakes are high for innovators to ensure that their inventions are robustly protected from the start. Justin Wilson, partner and cell & gene therapy sector specialist at Withers & Rogers discusses.
Cell and Gene Therapies
Allogeneic CAR T therapies are generating huge excitement due to their potential use as a cost-effective, readily available treatment for cancer. Unlike autologous CAR T therapies, which involve the extraction and modification of the patient’s own T cells, allogeneic therapies can be pre-prepared using a donor’s cells and be ready for use as and when required. As a result, allogeneic therapies are simpler and more cost-effective to produce, with the potential to be administered to the patient in a matter of hours, rather than waiting weeks for a bespoke treatment to be produced. Once these new ‘off-the-shelf’ therapies have secured the necessary regulatory approvals, they could become a new first-line treatment for cancer patients globally.
Whilst research and development activity is gathering momentum, and some early stage clinical trials are producing favourable results, some problems are yet to be fully resolved. As allogeneic therapies require the use of a donor’s cells, they can potentially trigger an immune reaction in the patient, so innovators are exploring ways to prevent this from happening. For example, some innovators are developing a form of viral protection to disguise the CAR T cells to prevent them from being attacked when they enter the patient’s body. Others are using CRISPR technology to modify the patient’s own immune cells, by blocking receptors, for example, to prevent them from rejecting CAR T cells entering the body.
Meanwhile, clinical trial activity for a number of allogeneic CAR T therapies is progressing at pace. Allogene Therapeutics Inc is currently conducting Phase 2 trials of an investigational allogeneic CAR T product, known as cemacabtagene ansegedleucel or cema-cell, as a potential first-line treatment for patients with large B-cell lymphoma (LBCL) who are among those most likely to relapse after first round chemoimmunotherapy. Phase 1 studies of the treatment have demonstrated a 58% complete remission (CR) rate in relapsed LBCL. Allogene also has four other allogeneic CAR T cell products in development.
San Diego-based, Fate Therapeutics Inc, is conducting a Phase 1 clinical trial of FT522 – its off-the-shelf CAR natural killer (NK) cell product candidate – in patients with relapsed or refractory B-cell lymphoma. This candidate is also the first to include alloimmune defense receptor (ADR) technology to resist host immune rejection. Recent market reports suggest that the NK cell therapy market is growing rapidly. Fate is also developing a number of preclinical CAR T cell products across autoimmune disease, hematological malignancy and solid tumor indications.
Also in the US, Caribou Biosciences Inc. is developing two allogeneic CAR T cell therapies CB-010 and CB-011. CB-010, an anti-CD19 CAR T, is undergoing Phase 1 clinical trials in patients with second-line large B-cell lymphoma. Data is expected to show later this year that its safety, efficacy and durability is on a par with approved autologous CAR T therapies. Its anti-BCMA CAR T cell therapy - CB-011 - is also undergoing Phase 1 clinical trials for patients with relapsed or refractory multiple myeloma.
With more allogeneic CAR T technologies entering early-stage clinical trials, intellectual property (IP) protection has an increasingly important role to play in securing the funds required to bring them to market. However, court decisions have not been helpful in some ways, particularly in the US, where the outcome of the Amgen Inc. v Sanofi case (2023), which centred on the protection of antibodies, could impact the patentability of other biologics, including CAR T cells. If unheeded, this issue could de-stabilise small biotech businesses involved in cutting edge R&D by impacting their ability to attract investment at a critical time.
Fortunately, help is at hand as IP strategists with an interest in allogeneic CAR T cell therapies have been working on ways to present the best commercial case possible to big pharma and other investors. Rather than drafting patent applications for novel CAR T technologies in isolation, for example, it is especially important to demonstrate that a holistic view of the marketplace is being considered, along with any jurisdictional differences that might apply. Understanding the implications of developing case law on a territory-by-territory basis is vital, as well as any subtle differences in the way individual applications are likely to be assessed. When preparing patent applications, a higher volume of varied data and an increased number and variety of examples will be needed to support a broad scope of claims, and to block potential workarounds by competitors.
In a dynamic marketplace, with investor interest in the development of first-line CAR T therapies peaking, the stakes are high for the biotech industry. Whilst investing in early-stage trials is essential to secure the data needed to justify their ongoing development, a considered IP strategy for each potentially life-saving CAR T therapy is needed to optimise its chance of success.