GP-1681

iStock, SiberianArt The prevalence of serious inflammatory safety issues such as cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome limits the reach of these transformative cancer therapies. This past summer, the FDA removed its Risk Evaluation and Mitigation Strategies designation for CAR T therapies. While the decision highlights how far these potentially curative therapies have come, only 30% of patients have access to CAR Ts. In order to unlock access, we must solve the toxicity problem. As a clinical pharmacist and biotech executive with more than 20 years of experience in healthcare, I’ve seen the transformative impact of CAR T—and the risks that can keep patients from fully benefiting from it. In my current role as CEO of CytoAgents, which develops therapies to manage cytokine-driven toxicities, I’m focused on finding safer, more-effective ways to mitigate CAR T’s most serious side effects. This role has given me a frontrow seat to observe why the FDA’s action is important, and what action is still needed. CAR T’s Promise and Perils CAR T therapy is one of the most transformative classes of medications in history, providing durable remissions at rates that have never been seen before in some cancers. For many patients, CAR T has been a therapeutic homerun. But it hasn’t been all good news. CAR T treatments involve reinfusing genetically engineered T cells to boost a patient’s antitumor response. Not surprisingly, juiced up T cells can produce inflammatory side effects such as cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). These are serious, potentially life-threatening events. By flooding the body with cytokines, CRS drives systemic inflammation. ICANS produces a similar response in the brain, generating inflammation that can cause neurological damage. For several years, the FDA placed a Risk Evaluation and Mitigation Strategies (REMS) designation on CAR T to better control these risks. REMS designations help ensure clinicians pay close attention to potential side effects, as well as carefully documenting their efforts to control them. CAR T has now been in hospitals for eight years, and clinicians are well aware of its potential toxicities and the associated mitigating strategies. The FDA decision to rescind the REMS designation will probably have no adverse impact on care and could alleviate some of the administrative burdens associated with the therapy. Cell therapy CAR T Guardrail Removal Earns FDA Favor with CGT Community Cell and gene therapy leaders say the agency’s decision to remove the Risk Evaluation and Mitigation Strategies that had been attached to approved CAR T cancer therapies reflects “thoughtful consideration of real-world evidence” and “regulatory trust.” July 1, 2025 · 6 min read · Heather McKenzie Still, as we applaud the REMS decision, we must refocus on the larger challenge: developing better treatments to control CRS and ICANS. These side effects are both serious and common. Around 70% to 95% of CAR T patients, and 40% to 60% of those receiving T cell engagers, develop CRS. Around 50% of patients treated with CAR T develop ICANS. Roughly 33% of patients who experience these side effects end up in an ICU. Patients with severe adverse events can be hospitalized for weeks, at total costs that can run over $500,000 each. Clinicians use intravenous corticosteroids and tocilizumab, a monoclonal antibody that inhibits interleukin-6, to fight CRS and ICANS. However, these treatments present their own risks, including serious infections and steroid-induced myopathies. We need better alternatives, and quickly. An Increasing Threat to Patient Access Despite the severity of these side effects, there has been limited investment in finding better ways to control them. In some ways, CAR T suffers from its own success, in that people tend to focus on the improved outcomes and minimize the potential risks. But it’s incredibly important that the biopharma industry take a hard look at what goes wrong with CAR T and develop better therapeutic responses. The need is tremendous. Setting aside the toll on patients and families, these side effects reduce access to this truly revolutionary therapy. Because CAR T is quite complex, and the toxicities are challenging to manage, the treatment has largely been limited to academic medical centers. This alone reduces access because many patients live hundreds of miles away from such a facility. Even academic hospitals must limit the number of patients they can accept for CAR T treatment due to its associated risks. Bed space is fixed, and patients who need care for CRS or ICANS can spend weeks in the hospital, often in the intensive care unit. This combination of limited beds and severe side effects creates a bottleneck that prevents many patients from accessing care. The obvious way to open up CAR T access is to make it available in community hospitals. This would largely remove the geographic barriers, as well as increase bed availability. However, before that happens, we need to develop better ways to manage CAR T’s toxicities through means that are easy to implement and fit readily into community hospitals and even outpatient settings. Specifically, the oncology community needs a safe oral treatment that reduces the need for steroids such as CTO1681, an oral steroid-sparing solution CytoAgents is trialing in the clinic. By better managing CAR T toxicities, we can get patients into outpatient and community hospital settings and expand access. This problem is only going to get bigger. Right now, CAR T is only being used in blood cancers, but there’s a concerted push to expand into solid tumors . There are currently hundreds of CAR Ts and T cell engagers in clinical trials. Some—possibly many—of these will be approved, exacerbating the need for CRS and ICANS solutions. Ultimately, by minimizing CAR T’s associated toxicities, we can open up bed space, move some of these therapies into outpatient and community settings and, most importantly, maximize patient access.

PITTSBURGH--(BUSINESS WIRE)--CytoAgents, Inc., a clinical-stage biotechnology company developing CTO1681, a novel, steroid-sparing inhibitor of prostaglandin-mediated inflammation announced today that data from two of its Investigational New Drug (IND) application enabling studies will be presented at the European Society for Medical Oncolgy (ESMO) Immuno-Oncology Congress 2025, taking place December 10-12, 2025 in London, United Kingdom. “We look forward to sharing these data at ESMO and to continuing our advancement of CTO1681," said Teresa Whalen, Chief Executive Officer at CytoAgents. CTO1681 is an orally administered immune modulator that targets inflammation in the tumor microenvironment and mitigates cell therapy induced toxicities frequently seen in lymphoma patients receiving CAR T-Cell Therapy. CytoAgents is currently enrolling patients in a Phase 1b/2a clinical trial evaluating CTO1681 in lymphoma patients receiving CAR T-Cell Therapy at risk for inflammatory driven toxicities. At ESMO, the company will present data from two non-clinical studies demonstrating that CTO1681 attenuates key cytokines known to drive Cytokine Release Syndrome (CRS) without compromising the CAR T-Cell mediated tumor killing in vitro and in vivo. These studies demonstrate that CTO1681 does not interfere with CD19 CAR T-Cell expansion and anti-tumor activity in vivo while reducing the inflammatory cytokines associated with CRS and ICANS. “These data suggest CTO1681 could enable safer CAR T-Cell Therapy administration, support outpatient treatment paradigms and broaden patient access without compromising anti-tumor efficacy,” said Teresa Whalen, Chief Executive Officer at CytoAgents. “We look forward to sharing these data at ESMO and to continuing our advancement of CTO1681.” Poster Presentation Details: Title: CTO1681 Does Not Interfere with CAR T-Cell Anti-Tumor Efficacy In Vivo Presenter: Michael Howell, PhD, Founder and President Mountaineer Biosciences, San Diego, CA, USA Final Poster Number (FPN): 109P Session Date and Time: Wednesday, December 10, 2025, 5:15 PM – 6:30 PM GMT Location: Queen Elizabeth II Centre – Churchill Room Title: CTO1681 Attenuates CRS-Driving Cytokines Without Compromising CAR T-Cell-Mediated Tumor Killing In Vitro Presenter: Michael Howell, PhD, Founder and President Mountaineer Biosciences, San Diego, CA, USA Final Poster Number (FPN): 113P Session Date and Time: Wednesday, December 10, 2025, 5:15 PM – 6:30 PM GMT Location: Queen Elizabeth II Centre – Churchill Room About CytoAgents CytoAgents, Inc. is a clinical-stage therapeutics company developing CTO1681, an oral, steroid sparing immunomodulator for multiple indications driven by cytokine inducing inflammation. By effectively reducing the inflammation in the tumor microenvironment and preventing life-threatening toxicities caused by overwhelming inflammation, CytoAgents is working to enable safer, widescale adoption of these breakthrough therapies. CTO1681 is currently in Phase 1b/2a for oncology patients receiving CAR T-Cell Therapy with plans to expand into additional therapeutic categories including asthma, COPD, and atopic dermatitis. www.cytoagents.com Forward Looking Statements Some of the statements in this press release may be forward-looking statements or statements of future expectations based on currently available information. Such statements are naturally subject to risks and uncertainties. Factors such as the development of general economic conditions, future market conditions, unusual catastrophic loss events, changes in the capital markets, changes in governmental regulations and other circumstances may cause the actual events or results to be materially different from those anticipated by such statements. CytoAgents does not make any representation or warranty, express or implied, as to the accuracy, completeness, or updated status of such statements. CytoAgents will not be liable to anyone for any decision made or action taken in conjunction with the information and/or statements in this press release or for any related damages.