Cullinan Therapeutics Announces Strategic Expansion Into Autoimmune Diseases & $280-Million Private Placement

Cullinan Therapeutics, Inc., formerly Cullinan Oncology, Inc. recently announced important updates about its plan to expand into autoimmune diseases, the scientific rationale for developing CLN-978 in autoimmune diseases, and initial clinical observations from its B cell non-Hodgkin lymphoma (B-NHL) study. In a separate announcement, the company also announced a $280-million private placement. The proceeds from the private placement, combined with current cash, cash equivalents, short term investments and interest receivable, are expected to fund Cullinan’s current operating plan into 2028.

Cullinan Therapeutics intends to pursue development of CLN-978 in autoimmune diseases, with systemic lupus erythematosus (SLE) as a first indication. The company believes that CLN-978 has the potential to be a first-in-class, off-the-shelf, disease-modifying treatment in autoimmune diseases with a differentiated safety profile​. The company plans to submit an investigational new drug application to study CLN-978 in patients with SLE in the third quarter of 2024 and is also planning for future development in other autoimmune diseases. The company has discontinued enrollment in its B-NHL study to focus ongoing development on autoimmune indications.

Recent data demonstrated the potential of CD19 directed CAR T therapies in the treatment of 15 patients with autoimmune diseases (systemic lupus erythematosus, idiopathic inflammatory myositis, systemic sclerosis). While the efficacy was notable, challenges could limit broad uptake of CAR T therapy, such as the requirement for lymphodepleting chemotherapy, risk of secondary malignancies, complex manufacturing processes, and limited patient access. CD19-directed therapies afford significant potential for the breadth of B cell depletion and the necessary immune reset, since CD19 expression occurs across all B lineage cells, including the short-lived plasma cells and plasmablasts that produce the pathogenic autoantibodies present in autoimmune conditions. The company believes that CLN-978 could offer a novel solution for patients and providers as a T cell engager designed to deliver potency with off-the-shelf convenience and subcutaneous dosing​.

On April 8, 2024, the Journal of Experimental Medicine published a Found in Translation article highlighting the potential advantages of CD19-directed T cell engagers to be superior to CD19 CAR-T cell engaging antibodies relative to CD19 CAR-T cells for the treatment of autoimmune diseases.

Clinical observations from three patients treated in a Phase 1 dose escalation trial of patients with B-NHL show that CLN-978 was clinically active at the initial starting dose of 30 μg administered subcutaneously once weekly. Two of the three patients experienced objective clinical benefit including one patient who experienced a complete response. Grade 1 cytokine release syndrome occurred in two patients and no patients experienced immune effector cell-associated neurotoxicity syndrome. Other adverse events were low-grade, manageable, or mechanistically based (eg, transient lymphopenia after the first dose only)​. Of the two patients with detectable B cells at baseline, both patients experienced rapid, deep, and sustained B cell depletion after administration of CLN-978. These data show that CLN-978 can deplete peripheral B cells and demonstrate clinical activity in a tissue resident disease at a dose with a favorable safety profile.

The corporate name change to Cullinan Therapeutics reflects the company’s transformation as it pursues new indications for autoimmune diseases and continues to advance its clinical-stage oncology pipeline. The new corporate name represents both the expanded therapeutic focus area and Cullinan Therapeutics’ vision to evolve to a commercial-stage biotech company. The company’s common stock will continue to trade under its current ticker symbol CGEM. Along with the new name, the company will adopt a new logo and will change its corporate website from www.cullinanoncology.com to  www.cullinantherapeutics.com.

“Today’s announcements represent a major step forward for Cullinan Therapeutics. Our ethos is to pursue the best science for patients by matching the right target with the right modality, and we believe that CLN-978 could offer a convenient modality and potentially disease-modifying treatment for patients with autoimmune diseases where current treatments often only address symptoms, rather than the underlying disease itself,” said Nadim Ahmed, Chief Executive Officer of Cullinan Therapeutics. “Our expertise in drug development and our robust financial resources, now with an additional $280 million through our recent financing activity, position us to execute and expand the development of CLN-978. We also plan to deliver multiple data catalysts from our ongoing oncology clinical programs throughout 2024. I look forward to continuing our positive momentum and I am proud of our team working relentlessly to deliver for patients in need.”

CLN-978 is a novel, highly potent, half-life extended CD19xCD3 bispecific T cell engager construct. CLN-978 potently triggers redirected lysis of CD19-expressing target cells in vitro and in vivo. CLN-978 is engineered to achieve very high affinity binding to CD19 to efficiently target B cells expressing very low CD19 levels. An HSA-binding domain increases the serum half-life of CLN-978 and, with subcutaneous delivery, permits more patient-friendly dosing and potentially reduced toxicity. CLN-978 contains two single-chain variable fragments (scFv), one binding with very high affinity to the CD19 target and the other binding to CD3 on T cells, and a single-domain antibody (VHH) binding to human serum albumin (HSA). CLN-978 was developed by an internal Cullinan team supported by co-founder and Scientific Advisory Board member Patrick Baeuerle, a world-renowned expert in the development of T cell engagers and CD19 biology and is a wholly owned asset. CLN-978 has the potential to offer a convenient, off-the-shelf therapeutic option for patients with autoimmune diseases such as systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disease in which the immune system attacks a patient’s own tissues. The most common manifestations of SLE include skin rashes, arthritis, swelling in the feet, and around the eyes, extreme fatigue, and low fevers. Lupus nephritis (LN) is a kidney disease and the most common severe manifestation of SLE. Approximately 40% of patients with SLE develop LN, which has a 10-year 30% mortality rate^3,4. SLE is more prevalent in women, people of color, and women of childbearing age. The CDC estimates the prevalence of SLE in the US to be approximately 160,000 to 320,000 cases. Currently available treatments do not routinely induce treatment-free remission, and most patients require lifelong immune suppression that treats symptoms without modifying the course of disease.

Cullinan Therapeutics, Inc. (Nasdaq: CGEM) is a biopharmaceutical company dedicated to creating new standards of care for patients. We have strategically built a diversified portfolio of clinical-stage assets that inhibit key drivers of disease or harness the immune system to eliminate diseased cells in both oncology and autoimmune diseases. Our portfolio encompasses a wide range of modalities, each with the potential to be best and/or first in class. Anchored in a deep understanding of oncology, immunology, and translational medicine, we create differentiated ideas, identify the most appropriate targets, and select the optimal modality to develop transformative therapeutics across a wide variety of cancer and autoimmune indications. We push conventional boundaries from candidate selection to differentiated therapeutic, applying rigorous go/no go criteria at each stage of development to fast-track only the most promising molecules to the clinic and, ultimately, commercialization. With deep scientific expertise, our teams exercise creativity and urgency to deliver on our promise to bring new therapeutic solutions to patients.