Mosperafenib

Roche may have scrapped work on a T-cell engager (TCE) for lupus, but the company’s head of pharma told Fierce that the drugmaker still has a strategy for developing cell therapies for autoimmune diseases. As part of a wider pipeline clearout disclosed during Roche’s second-quarter earnings results released July 23, the Swiss pharma revealed that it had stopped work on RG6382, a T-cell-engaging bispecific antibody targeting CD19 and CD3. The company had been evaluating the therapy in an ongoing phase 1 open-label study of patients with systemic lupus erythematosus (SLE). But a Roche spokesperson explained to Fierce this morning that after reviewing the data to date, “it has become clear that this molecule does not have the requisite characteristics to move forward in this indication.” “Since SLE was the lead indication for this asset, this discontinuation marks the termination of its development,” the spokesperson added. Autoimmune diseases have become a popular target for cell therapies in recent years —most notably CAR-T therapies, where Kyverna Therapeutics may potentially be first to market with mivocabtagene autoleucel for stiff person syndrome. When Roche struck a $1.5 billion deal to buy Poseida Therapeutics in 2024, the pharma referenced the potential of using the biotech’s cell therapy pipeline, including a BCMAxCD19 CAR-T, to treat autoimmune disease. On a call with journalists this morning, Roche Pharmaceuticals CEO Teresa Graham acknowledged to Fierce that autoimmune disease “was indeed one of the aspects of the Poseida deal.” When asked by Fierce whether Roche is still exploring the potential of cell therapies to treat these diseases, Graham said: “Yes, we do intend to continue development, and we hope to be able to provide some more updates soon.” Today’s pipeline clearout included two drugs in phase 2 development. One of these was CT-868, a once-daily, dual GLP-1/GIP receptor agonist for Type 1 diabetes that Roche had acquired as part of its buyout of Carmot Therapeutics. Despite seeing positive phase 2 data for CT-868, Roche has decided to prioritize another Carmot asset—a once-weekly GLP-1/GIP agonist called enicepatide—for T1D instead. As enicepatide is also being evaluated for obesity, it “makes more sense” for Roche to focus on this program, executives explained on the earnings call. “We believe enicepatide has best-in-disease potential for glycemic control and can deliver maximum therapeutic differentiation for patients living with diabetes,” a spokesperson told Fierce. “Further details regarding our plans for enicepatide in T1D will be shared at a later stage.” The other mid-stage asset thrown on the scrap heap was an anti-Tie2 agonist dubbed RG6351. Roche had been assessing the therapy in the eye disease diabetic macular edema (DME) as both a monotherapy and in combination with Eylea or Vabysmo. However, a look at the data showed a “low probability” of beating Vabysmo, a spokesperson told Fierce. The study “reinforce[d] that dual inhibition of VEGF/Ang-2 with [Vabysmo] is thought to provide robust activation of the Tie2 pathway for patients with DME,” they added. Further back in Roche’s pipeline, the company discontinued a clutch of phase 1-stage drugs. Aside from the TCE, these included mosperafenib, a BRAF inhibitor that was being evaluated for solid tumors. That trial closed in April, a spokesperson told Fierce. “While data from the phase 1a/b trial has shown to be positive, we believe that licensing out this asset to a suitable partner would be the best path forward for this asset and for the wider community,” they added. Mosperafenib was joined on the discard pile by another solid tumor candidate in the form of RG6468, which was being assessed in combination with Tecentriq. Roche didn’t confirm RG6468’s mode of action, but did tell Fierce that the company had decided to halt the program after reviewing the phase 1 data. The company’s second-quarter earnings also reaffirmed Roche’s decision earlier this month to scrap two of its Huntington’s disease prospects , including the phase 2-stage tominersen, which was partnered with Ionis Pharmaceuticals.