KROS - Keros Therapeutics: Undercovered Company With Data From All Programs

2023-04-30 08:07:34 ET

Summary

• KROS is a small company with three clinical programs.
• Surprisingly, each program has clinical data.
• The company is well funded, with good data, and I find it interesting.

Keros Therapeutics ( KROS ) is a small-to-medium size company with three clinical programs in hematology and other indications, each of which has produced clinical data, a fact that makes the company interesting. Their focus is on modifying growth factor-beta (TGF-?) signaling in order to produce therapeutic benefit in blood cells, blood vessels and heart tissues.

The pipeline is this:

Lead candidate KER-050 is an investigational activin receptor type IIA (ActRIIA) fusion protein designed to inhibit select TGF-? ligands, including activin A. The company mentions a Phase 1 clinical trial at ASH 2020 and elsewhere. I cannot find a reference to this trial in the registry . Anyway, Keros says:

…administration of KER-050 to healthy volunteers led to robust, rapid and sustained increases in red blood cells (RBCs), hemoglobin ((HGB)) and platelets, supporting an effect on the multiple stages of hematopoiesis.

There is a phase 2 trial ongoing, and we seem to have some data from here as well. The trial is for Anemia and Thrombocytopenia in patients with Myelodysplastic Syndromes. The molecule was generally well-tolerated. There were three TEAEs leading to treatment discontinuations: injection-site reaction (related); dyspnea (unrelated); chronic obstructive pulmonary disease (unrelated). So only one was treatment-related, and the other two were unrelated to the drug.

In terms of efficacy, sustained transfusion independence was observed in a number of patients with RP2D, or the dose selected. Mean duration was 196 days, and 53% of patients had such transfusion independence at ?12 weeks. This was observed in both ring sideroblasts positive and negative patients regardless of initial transfusion burden.

Now, in this patient population, current treatment options for symptomatic anemia include red blood cell ((RBC)) transfusions, erythropoiesis-stimulating agents (ESAs) and Reblozyl. Each of these options has problems. ESA is only beneficial for patients with low transfusion burden. This is also true for reblozyl, which is approved to treat only RS+ patients. In trials, only 20% of high transfusion burden patients achieved TI at 8 weeks compared to 4% in placebo. That exact number, in RS+ patients in the KER-050 trial, was 45.5%, and for RS- patients, it was 60%. While this is an open label trial from which no certain conclusion can be drawn, the numbers are certainly impressive. RBC transfusion is the gold standard, however it also produces iron overload and can cause AML, reducing overall survival. KER-050 addresses these problems, and it has done well enough to merit further study.

Another phase 2 trial is ongoing of KER-050 as monotherapy or in combination with ruxolitinib to treat anemic patients with MF. Early data shows the drug was generally well-tolerated. As for efficacy :

Although variability was observed amongst the patients, treatment with KER-050 at the lowest dose in this trial (0.75 mg/kg) resulted in increased reticulocytes and platelets on aggregate, both as monotherapy and in combination with ruxolitinib, and regardless of transfusion status.

Their second candidate is KER-047, a novel, oral small molecule inhibitor of activin receptor-like kinase-2 (ALK2) that helps suppress hepcidin expression and mobilize iron for incorporation into hemoglobin. Indications targeted are anemia in patients with Iron-Refractory Iron Deficiency Anemia ((IRIDA)) and Functional Iron Deficiency ((FID)) in MDS and MF.

In a phase 1 trial, KER-047 treatment reduced Hepcidin levels and increased Hemoglobin content in Reticulocytes. There were no serious adverse events, and the treatment was generally well-tolerated.

The third clinical candidate is KER-012, a modified activin receptor IIB ligand trap designed for Pulmonary Arterial Hypertension ((PAH)) and other Cardiovascular Disorders. In a phase 1 trial in healthy volunteers, the molecule was well-tolerated and was shown to inhibit activin signaling at a molecular level.

Financials

KROS has a market cap of $1.29bn and a cash balance of $279mn. Research and development expenses were $24.9 million for the fourth quarter while general and administrative expenses were $7.1 million. At that rate, the company has cash for more than 2 years.

The company was launched with funds from OrbiMed, Venrock and Cowen. KROS insider transactions data shows it is regularly sold, sometimes outright sales, and sometimes option exercises; there’s only one buy in the last two years, and that too, the latest transaction.

Bottomline

I find KROS interesting and a potential speculative buy. This is an overview article where I simply familiarize myself and my readers with a less-known company. I haven’t discussed many things, like valuation, for example, or market potential. The market is admittedly large, but to figure out the actual target market will need another article, which I will do if the molecules here continue to interest me. Meanwhile, the stock is trading at a 30% discount to its 52-week highs, and while it is very far from its 52-week low, I might begin a pilot position in order simply to be able to follow the company better.

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