Biomea tries something new in diabetes
An unusual mechanism shows promise, but competing will not be easy.
Almost all developers of menin inhibitors are positioning their projects as cancer therapies. The exception, Biomea Fusion, yesterday posted data that begin to justify its exploration of this mechanism in diabetes – and doubled in value as a result.
But type 2 diabetes is the arena of behemoths. Ozempic and Mounjaro are both forecast to have peak sales in excess of $10bn, and seven more non-insulin agents are forecast to be blockbusters by 2028. Biomea, whose market cap is less than $1bn even after yesterday’s increase, surely cannot contest this market alone.
The mechanistic rationale for menin blockade in diabetes rests on the belief that the protein reduces beta cell turnover and growth in the pancreas; inhibition of this could therefore lead to regeneration of healthy insulin-producing beta cells. This potential for a disease modifying treatment for diabetes seems to have excited investors.
Yesterday’s data came from the two cohorts in the phase 2 portion of Biomea’s Covalent-111 trial – cohort 1, consisting of 16 healthy volunteers, made up the phase 1 part of the trial. Cohorts 2 and 3 each consisted of 12 patients who had been diagnosed with type 2 diabetes at least 15 years earlier, and whose condition was poorly controlled despite treatment with up to three antidiabetic medications. The patients had BMIs between 25 and 40kg/m2, making them overweight or obese, though not morbidly so.
In cohorts 2 and 3, 70% and 89%, respectively, of patients given Biomea’s menin inhibitor BMF-219 for four weeks experienced reductions in their blood sugar. But so did 50% of placebo patients across both cohorts, and no claims for statistical significance were made.
Tolerability across all three cohorts was good, with no dose reductions, serious or severe adverse events, or discontinuations.
The magnitude of the cuts in blood sugar were encouraging on a cross-trial basis. In one of Mounjaro’s pivotal diabetes trials, Surpass-2, in which the GIP/GLP-1 inhibitor was used in combination with other diabetes therapies, the HbA1c reduction at the four-week mark was approximately 0.75-1.0 with the highest dose.
But, as Stifel analysts pointed out, Biomea’s trial was short, the sample size was small, and the patients’ background treatments were not fully balanced, which makes it had to tease out BMF-219’s effect.
Covalent-111 is continuing, with future patients to be dosed at higher levels, and Biomea also plans to evaluate longer dosing periods. This research will be crucial to seeing whether the company can continue dodge the more worrying potential side effects of menin inhibition, which include neoplasms and the differentiation syndrome that caused an early trial of Kura Oncology’s menin inhibitor in leukaemia to be halted in 2021.
Biomea intends to look at BMF-219 in other diabetic populations, including type 1 diabetes, the company said.
The company gave no details on its plans for later-phase development of the product. But phase 3 diabetes trials generally involve enrolling a couple of thousands of patients, and it is not clear that Biomea could afford such an undertaking by itself. Asked on a conference call yesterday whether the group was considering partnering on the product, management simply said that it would continue the phase 1/2 trial and then try to understand that “the optimal path forward would look like”.
Investors are clearly keeping faith: Biomea announced a $125m share offering today, yet its stock is up a further 16% in early trade.