Cullinan developing treatment for lupus, other autoimmune diseases

US oncology drug developer expands focus to include autoimmune diseases

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by Mary Chapman |

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Note: This story was updated May 6, 2024, to correct that Cullinan Therapeutics continues to pursue its oncology platform while also expanding into treatments for autoimmune diseases including lupus.

Cullinan Therapeutics has announced its plans to exclusively pursue the development of its T-cell-engager CLN-978 as a treatment for autoimmune disorders, beginning with systemic lupus erythematosus (SLE).

The goal, according to the company, is to transform CLN-978 into a safe, first-in-class disease-modifying therapy.

The Massachusetts-based biopharmaceutical, formerly known as Cullinan Oncology, intends to submit an investigational new drug application to the U.S. Food and Drug Administration later this year seeking authorization to test CLN-978 in patients with SLE, the most common form of lupus, Cullinan said in a press release.

The company noted that it also plans to develop the subcutaneous, or under-the-skin, injectable treatment candidate for other autoimmune conditions.

“Today’s announcements represent a major step forward for Cullinan Therapeutics,” said Nadim Ahmed, the company’s CEO. “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.”

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Cullinan says CLN-978 has potential to be ‘first-in-class’ treatment for lupus

In lupus, the immune system attacks the body’s own tissues, resulting in a broad range of symptoms. As part of the autoimmune attack, B-cells — a type of immune cell — make antibodies, known as autoantibodies, that wrongly target healthy tissues.

The primary goal of lupus treatment is to mitigate the autoimmune response that causes the disorder, control its symptoms, and prevent organ damage.

CLN-978 is a new and highly potent T-cell engager that’s designed to redirect immune T-cells to attack and kill the B-cells that drive lupus. T-cell engagers are specialized antibodies that are engineered in a way to redirect T-cells to recognize and attack certain types of cells, including cancer cells.

The treatment is able to do so by simultaneously binding to CD19 — a protein found on the surface of B-cells — and to CD3, a protein that plays a key role in T-cell activation.

As a novel, highly potent, half-life extended CD19 x CD3-bispecific T cell-engager, CLN-978 has the potential to be a first-in-class, disease-modifying treatment in autoimmune diseases with a differentiated safety profile.

CLN-978 also has a specific domain that allows it to interact with a protein called albumin that’s highly stable in the bloodstream. This specific interaction increases the therapy’s half-life, or the time it takes for its levels to drop to half of those originally administered, allowing it to remain active in the body for longer periods of time.

“As a novel, highly potent, half-life extended CD19 x CD3-bispecific T cell-engager, CLN-978 has the potential to be a first-in-class, disease-modifying treatment in autoimmune diseases with a differentiated safety profile,” Jeffrey Jones, MD, Cullinan’s chief medical officer, said in an emailed statement to Lupus News Today.

CD19-targeted CAR T-cell therapies, which have recently shown promise for the treatment of lupus and other autoimmune disorders, also work by a similar principle, relying on the use of T-cells that have been engineered in the lab in a way to ensure they specifically recognize and destroy B-cells containing CD19 on their surface.

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Some challenges remain for CAR T-cell therapies use in autoimmune diseases

Despite their therapeutic potential, there are still a few challenges that can limit the adoption of CAR T-cell therapies as a treatment for autoimmune diseases. These include their complex manufacturing process, the need for patients to undergo chemotherapy prior to receiving treatment, and the risk of cancer.

“We believe CLN-978 could offer a novel solution for patients and providers as a T cell engager designed to deliver similar potency with off-the-shelf convenience, subcutaneous dosing, no need for lymphodepleting chemotherapy, and no expected risk for secondary malignancies,” Jones said.

To focus its development on autoimmune indications, Cullinan has ceased enrolling patients in its open-label Phase 1 study (NCT05879744) of CLN-978 in patients with hard-to-treat B-cell non-Hodgkin lymphoma, a type of blood cancer.

Two of three patients treated in the trial were observed to have experienced clinical benefits. Following CLN-978 administration, two patients with detectable B-cells at the study’s start experienced rapid, deep, and sustained B-cell depletion. CLN-978 also was found to have a favorable safety profile.

Ahmed said the company is eager to move forward, and noted recent company financing that raised $280 million.

“Our expertise in drug development and our robust financial resources … position us to execute and expand the development of CLN-978,” Ahmed said, noting that the Cullinan also plans “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,” Ahmed added.