Keros Monetizes Hematology Asset In Deal With Takeda

Keros Therapeutics has secured Takeda as a partner for one of its two mid-stage drug candidates, allowing the company to extend its cash runway and focus R&D investment on the other. The companies announced a licensing deal on 3 December in which Takeda will pay $200m up front in cash for rights to elritercept, an active receptor type IIA fusion protein designed to inhibit select transforming growth factor-beta (TGF-β) ligands in Phase II development for hematology indications.

The deal allows Keros, which specializes in developing drugs for disorders linked to dysfunctional signaling of TGF-β proteins, to focus on another mid-stage asset, cibotercept, which is in Phase II testing for pulmonary arterial hypertension (PAH).

“Knowing that we were working the TGF beta pathway, where I have been working for many decades, I knew we were going to end up with therapeutics that were going to be in numerous diverse indications and we would not have the resources to commercialize every single opportunity,” Keros CEO and co-founder Jasbir Seehra said in an interview.

Seehra has a lot of credibility working in this area of biology. He was co-founder and chief scientific officer at Acceleron Pharma, where he was a co-inventor of two now marketed drugs that work through the TGF-β pathway: Rebloyzl (luspatercept), owned by Bristol Myers Squibb, and Winrevair (sotatercept), owned by Merck & Co., which acquired Acceleron for $11.5bn in 2021.

At Keros, elritercept and cibotercept aim to improve upon the standard of care advanced by Rebloyzl and Winrevair in their respective therapeutic areas, anemia in hematological malignancies and PAH.

Reblozyl was approved by the US Food and Drug Administration in 2019 to treat anemia in beta-thalassemia patients but has gained additional indications since, including anemia in patients with myelodysplastic syndromes (MDS). Winrevair (sotatercept) was approved by the FDA for PAH in March.

“We could not afford [the] resources – both capital and human – to commercialize both indications at the same time,” Seehra said of the two Keros programs advancing through the clinic at the same time. “Therefore, we knew that we would have to partner one or the other. We could be a hematology company, we could be a PAH company, but we can’t be both at the same time.”

Takeda Wins A Competitive Process

Elritercept is slightly ahead of cibotercept in development. It is being tested in two Phase II clinical trials, one in patients with very low-, low- or intermediate-risk MDS and one in patients with myelofibrosis. The company presented encouraging data from a low-dose cohort of patients from the MDS trial at the American Society of Hematology meeting last year, and the Phase III RENEW trial evaluating elritercept in adults with transfusion-dependent anemia with very low-, low- or intermediate-risk MDS is expected to begin enrollment soon following feedback from the FDA.

“Earlier this year, we had the end-of-Phase II discussion and the FDA provided clear perspective on what the registration trial could be and therefore we always knew that this could be a catalyst for some partners, where they see the program as being sufficiently de-risked,” Seehra said.

The licensing deal was competitive, he said, with multiple bidders, but Takeda stood out because of its shared vision for a broad development program behind elritercept, he said.

“Takeda came out of the gate believing that, based upon the data, that it is differentiated from luspatercept,” he said. “We believe that it is differentiated but now [we] have a partner that also believes it is differentiated.”

In addition to MDS and MF, Seehra said Takeda shares a vision to explore additional indications for elritercept, ranging from additional anemias to kidney disease.

“Takeda is 100% aligned with our vision and they have the commercial depth, capital and people to be able to explore all these potential indications,” he said.

Under the deal, Takeda gains rights to elritercept worldwide, except for in mainland China, Hong Kong and Macau. Takeda will be responsible for development, manufacturing and commercialization. Keros is eligible to receive development, approval and commercial milestone payments that could exceed $1.1bn plus tiered royalties on net sales.

Analysts felt the deal made strategic sense for Keros.

“Elritercept’s data to date suggests differentiation from Reblozyl (peak sales estimates $3bn+) with duration of response being a key upside driver to revenue estimates,” Wells Fargo analyst Tiago Fauth said in a same-day note. “However, given a long development path in front-line MDS and increased competition in addition to greater focus on cibotercept as the main upside driver, few investors assigned value to the program. In that context, the narrower focus going forward and extended runway are clear positives for Keros.”

The cash from the deal will allow Keros to extend its already solid financial footing. The company said it expects the Takeda investment will extend its cash runway into the fourth quarter of 2028 while funding the development of cibotercept and an earlier-stage pipeline asset, KER-065, which is in Phase I development for obesity and neuromuscular conditions. Keros reported having cash and equivalents of $530.7m as of 30 September.

Investors will be closely watching the main catalyst for cibotercept, the data read out from the Phase II TROPOS trial in PAH, which is fully enrolled and expected to read out in the second quarter.

The company has high hopes for cibotercept, which it believes will be differentiated from Winrevair because the design of the molecule allows for a higher therapeutic index, which could improve both efficacy and safety. Winrevair comes with a risk of bleeding and requires platelet monitoring, a side effect that Keros hopes to avoid with cibotercept.