Acute Myeloid Leukemia(AML) is one of the deadliest and most difficult blood cancers to treat. It accounts for about one in three adult leukemia cases and about 1% of all cancers, yet progress in survival outcomes has been painfully slow. Treatment options remain limited, and relapse rates are high. A first-in-human Phase 1/1b clinical trial that began in early 2025 is hoping to change that treatment paradigm.

CERo Therapeutics is developing a completely novel approach to treating various types of cancer, starting with AML. T cells have specialized functions for killing targeted cells, showcased by the natural working of the human body’s immune system. CERo’s platform takes a patient’s own immune cells and re-engineers them to create macrophage-like capabilities that can target and eliminate cancer cells. Macrophages are white blood cells that engulf and digest pathogens, including cancer cells. By combining the forces of cell killing (T-Cells) and phagocytosis (Macrophages), CERo’s unique CER-T-Cells overcome the limitation of existing therapies to selectively target patients own specific cancer cells leading to a potentially safer and more efficacious means of cancer treatment.

CERo’s first-in-human trial is now underway, with dosing already started and initial patient data showing positive results. The study is being held across three separate trial sites across Texas, Colorado, and Tennessee, with The University of Texas’ MD Anderson Cancer Center dosing the first patient. The open-label trial will evaluate CERo’s lead candidate CER-1236 in patients with AML that is either relapsed/refractory, or in remission with measurable residual disease, or newly diagnosed patients with TP53 mutated MDS/AML. The trial has started with dose escalation to establish safety and optimal dosing, followed by an expansion phase to assess early signs of efficacy. Additionally, CER-1236 was recently granted orphan drug designation by the US FDA.

The Company isn’t going to stop there. In preclinical data, CERo has demonstrated tumor-killing capabilities in both liquid and solid cancers, and in parallel, the team plans to initiate trials in ovarian and non-small cell lung cancers before the end of this year in a similar fashion to the AML trial. Drug Development & Delivery recently interviewed Chris Ehrlich, CEO of CERo Therapeutics, to discuss the company’s science, clinical program, the treatment landscape, and more.

Q: Can you tell us a little bit about CERo Therapeutics?

 A: CERo Therapeutics is a clinical-stage company founded in 2016 with the goal of expanding the potential of engineered T cell therapy into hard-to-treat cancers by merging aspects of the innate and adaptive immune system into a single cell. This idea led to the development of CER-T technology, which combines traditional CAR-T signaling components that harness the potency of the T cell with an innate immune receptor binding domain and signaling domains that allow the T cell to “see” and “eat” tumors like an innate phagocyte would.

Q: How does CERo’s CER-T technology platform work, and how is it different from traditional CAR-T therapy?

A: CER-T cells work by redirecting a patient’s own T cells so that they can recognize and kill cancer cells. What makes CER-T cells unique compared to traditional CAR-T therapy is twofold. First, CER-T cells target TIM-4-L, a novel target that hasn’t been investigated in cell therapy. TIM-4-L is frequently overexpressed on malignant cells, such as AML, ovarian cancer, or NSCLC, but is absent on healthy cells. We believe this pattern of expression will enable CER-T cells to be exquisitely focused against cancer with minimal off-target toxicities. Second, CER-T cells have been designed with the ability to phagocytose target cells, which is not a typical function of T cells. This gives the cells a second mode of anti-tumor killing that complements the traditional mechanisms of T cell-mediated killing. Interestingly, CER-T cells can even act as antigen-presenting cells after phagocytosis, potentially allowing them to bolster this critical immune function that is frequently dysregulated in the tumor microenvironment.

Q: What indications have you targeted for this type of treatment to date and do you expect this to be applicable to more indications in the future?

A: Currently, we are targeting AML, ovarian cancer, and non-small cell lung cancers. These diseases have high unmet need and have been difficult to target with engineered T cells, and express high levels of TIM-4-L making them ideal candidates to test CER-1236. However, we have observed TIM-4-L expression on a wide range of other cancer types and are excited to determine if CER-1236 has pre-clinical anti-tumor effect in these cancer types to support expanding what indications CER-T cells might treat in the future.

Q: Can you tell us about the progress of CERo’s current clinical programs?

A: Since the acceptance of CERo’s AML IND, we’ve moved quickly to onboard three sites and a number of CROs to initiate our trial. We’ve successfully treated four patients to date in the dose escalation phase and those patients are being carefully monitored for safety and efficacy. We plan to share more data as the trial progresses. In the meantime, we are gearing up to initiate our second clinical trial in solid tumors, including ovarian and non-small cell lung cancer, and are working to expand our manufacturing capacity to support these trials through future phases.

Q: What makes this new type of T cell therapy so exciting for your clinical team and partners like MD Anderson?

 A: The great success of CAR-T cell therapies in B cell malignancies has been difficult to translate into other indications, including AML. Because the cancerous cells in AML share so many cell surface markers with healthy bone marrow progenitor cells, off-target toxicity has been a frequent problem. Additionally, recent work suggests that AML blasts have mechanisms that confer some resistance to T cell killing. The innovation of engineering an additional killing mechanism, phagocytosis, allows CER-T cells kill a cancer cell via multiple non-overlapping adaptive and innate mechanisms, which we believe will overcome some of resistance seen in AML. The selection of TIM-4-L as a target is also a novel and very promising feature of CER-T cells. TIM-4-L is a class of ligand that has never been targeted by cell therapy, and the biology of TIM-4-L really restricts its expression to cancer cells, while healthy cells avoid expressing it. We believe this will reduce the off-target toxicities that have been stymied AML CAR-T therapies in the past.

Q: What should we expect to see from CERo Therapeutics over the next two to three years?

A: CERo is very positive about the potential for CER-T cells, and we are fortunate to be starting our initial clinical trial at doses that could functional and therapeutic. For AML, we are investigating subsets with defined paths to FDA approval. We hope in two to three years we will be pursuing pivotal trials or FDA approval for CER-T cells in AML and potentially solid tumors shortly after, and initiating trials in other indications, including rare cancers without good CAR-T targets, to expand the application of the CER-T technology.