Q&A: Novel immunotherapy is poised to tackle multiple cancers

Chimeric antigen receptor (CAR) T-cell therapy is a form of medical treatment where a patient’s T cells (a type of immune cell) are changed in the laboratory and then administered back to the patient so they will bind to cancer cells and kill them. Such biotechnology represents a source of innovation for the medical world.

Chris Ehrlich, CEO of CERo Therapeutics Inc. (Nasdaq: CERO), a leading immunotherapy company advancing the next generation engineered T Cell therapies for the treatment of cancer. Digital Journal asked Ehrlich about the technology and development curve.

Digital Journal: Can you provide a brief background on CERo Therapeutics?

Chris Ehrlich: CERo Therapeutics is an emerging biopharmaceutical company that is developing a pioneering approach to treat liquid and solid tumors.  By equipping a patient’s own T cells with a hybrid receptor using components of the innate immune system’s phagocytic machinery, we give T cells a novel ability to interact with and activate the immune system against the cancer cells, which is a process that is commonly dysregulated in cancer.

After more than half a decade of work, CER-1236, our lead product, is poised to enter the clinic in patients with Acute Myeloid Leukemia and Ovarian and Non-Small Cell Lung Cancers.

DJ: How does CERo’s CER-T technology platform work?

Ehrlich: CERo’s technology works by grafting onto patients’ own T-cells a receptor that binds to a naturally occurring human antigen that is upregulated in cancer cells.  The exquisite selectivity of this antigen on cancer vs healthy cells allows us to deliver a highly targeted therapy utilizing a patient’s own immune system which should result in massively efficient cancer cell killing with limited collateral damage.  In addition to the novel target, CER-1236 combines two of the human bodies’ most efficient killing mechanisms in that it both lyses and phagocytoses the tumor cells providing a double-barreled approach.

DJ: What technologies were pivotal to the development of CERo’s therapy?  

Ehrlich: CERo Therapeutics and our candidate, CER-1236, builds upon more than half a decade of work from our leading clinical team. Here are a few of the milestones that have been pivotal to getting us to where we are today:

1. The perfection of using lentiviral vectors to transfect cells allowed for efficient “loading” of the key payload of CER-1236
2. Recent improvements in manufacturing technologies have allowed for a time and capital efficient manufacture of CER-1236
3. The improvement in sample collection and transport logistics for other CAR-T therapies allows for general acceptance of the autologous approach and the ability to capitalize on efficiencies involved with related products

DJ: Why did CERo choose Acute Myeloid Leukemia as one of the first indications for this kind of treatment?

Ehrlich: AML is a deadly disease with limited treatment options.  In some forms of the disease, traditional chemotherapeutics make the disease worse.  We chose AML for several reasons:

1. We recently generated compelling preclinical data showing that the target of CER-1236, the TIM-4 Ligand, is highly expressed on AML cells
2. The publication of this data attracted the attention of a thought-leading physician who reached out to the company to express his desire to test CER-1236 in his end-stage patients who had no other options; we believe that patient enrollment will be robust and quick
3. The unmet need in AML is enormous and thus the resulting economic opportunity is substantial
4. The FDA recognized all of the above and allowed us to test our first-in-human trial in actual AML patients and start at potentially therapeutic doses; this will allow for a rapid readout to see if the drug works as expected
5. The path to potential registration for a novel cell therapy in AML is quick and relatively inexpensive compared to other drugs which potentially gives CERo the chance to control its own destiny without needing a large strategic partner.

DJ: What is different about CERo’s approach compared to traditional cancer treatment?

Ehrlich: CER-1236 is an autologous cell therapy.  This is fundamentally different that other types of cancer treatment, including chemotherapy, monoclonal antibodies, and targeted small molecule drugs. 

While T-cell therapies have become increasingly prominent in treating cancer, some of the major issues plaguing the development of engineered T cells have been the lack of good targets that are on the tumor and not on healthy cells, and the many immunosuppressive strategies cancers employ that impair immune responses to them. By targeting TIM-4 Ligand, an immunosuppressive marker that healthy cells are evolutionally designed to not express, but cancers often overexpress, we can retarget T cells to many types of cancer and have a robust data package suggesting it won’t target healthy cells. Additionally, by engineering in the ability to phagocytose cancer cells, we allow the CER-1236 T cells to act as macrophages or dendritic cells, which are often dysfunctional in cancers, and hopefully restore that vital immune function in the tumor microenvironment. 

Most CAR T cells on the market or under development rely on an antibody fragment, or scFV, to retarget the T cell to an antigen. The scFV doesn’t have much function outside of that retargeting and can only retarget cells to that specific antigen. Because of the diversity of cancer types, there’s often a limited number of cancers that can be targeted with any given scFV, and off-tumor toxicity is always a concern. What is novel about CER T cells is that our binding domain is TIM-4, a natural human protein that by itself can bind TIM-4 Ligand and mediate phagocytosis. By adding TIM-4 binding domain to some more canonical CAR T signaling domains, we can retarget CER-1236 T cells to the TIM-4 Ligand that is present on a wide range of tumor types, and give the T cells not only the ability to kill and proliferate in response to the cancer, but also the macrophage-like ability to eat and present cancer antigens to the non-edited immune system.

DJ: What clinical milestones does CERo expect to have this year? 

Ehrlich: Our lead asset, CER-1236 has impressive data in multiple preclinical models of cancer.  The FDA has approved for us to start dosing patients in AML, so the next milestone will be dosing the first AML patient.  Another milestone we expect is approval to start dosing patients with solid tumors, specifically Lung and Ovarian cancer.