Keros Therapeutics: Interesting Early Data From A Promising Molecule (Downgrade) (KROS)

In April, I covered Keros Therapeutics, Inc. (NASDAQ:KROS), and found it interesting. Keros had three published datasets from three clinical-stage programs. The stock had a short rally after my coverage, then went down, took another small leap, and then went down again after announcing more data from its lead program. It has now recovered back to the April levels, and so I want to take another look at it.

Keros works by disrupting growth factor-beta (TGF-β) signaling to produce therapeutic effects on blood cells, blood vessels, and heart tissues. It has 3 programs in hematology and pulmonary and cardiovascular diseases, each of which has produced clinical data. The lead asset is KER-050, an investigational activin receptor type IIA (ActRIIA) fusion protein that inhibits select TGF-β ligands, including activin A. I discussed phase 2 data in patients with Anemia and Thrombocytopenia where they have Myelodysplastic Syndromes. There was sustained transfusion independence in a number of patients with the selected phase 2 dose. The mean duration was 196 days, with 53% of patients having transfusion independence at ≥12 weeks. This was observed in both ring sideroblasts positive and negative patients, regardless of initial transfusion burden.

Looking at the company’s November presentation, there are two trials whose data we have (as of December). One is for KER-050 monotherapy to treat Anemia due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes or MDS. The other is KER-050 alone OR in combination with ruxolitinib to treat myelofibrosis or MF. Both are phase 2 trials.

Now, for the MDS trial, the status as of April 3, 2023,:

▸ Part 1 Dose Escalation (N=31; completed)

▸ RP2D: 3.75 mg/kg with the ability to titrate to 5 mg/kg Q4W

▸ RP2D experienced patients: N=59

▸ 25 patients from Part 1

▸ 34 patients from Part 2.

There were two fatal TEAEs at this time, however, they were deemed unrelated to treatment.

Across a broad population of low-risk MDS patients, the following data emerged by April:

Click to enlarge

Here, HTB refers to high transfusion burden patients. RP2D is, of course, the recommended phase 2 dose, which is 120 mg. Key points:

Erythroid Response is a positive change in red blood cell parameters. The response is measured as Hematologic Improvement in Erythropoiesis (HI-E) or Transfusion Independence (TI). In the “All evaluable patients” group, 51.4% (19 out of 37) showed an overall Erythroid Response. In the “HTB evaluable patients” subset, the response rate is 50% (11 out of 22).

IWG 2006 HI-E Response:

HI-E response is based on criteria outlined by the International Working Group (IWG) in 2006.

Similar to the overall response, both the entire evaluated population and the subset show a 51.4% response rate.

TI ≥8 weeks:

TI refers to Transfusion Independence, and this metric is measured for a duration of at least 8 weeks.

In the larger group, 42.3% (11 out of 26) achieved TI for the specified duration.

In the subset, the TI rate is 40.9% (9 out of 22).

RS+ (Reduction in Transfusion Burden):

RS+ refers to ring sideroblast positive patients who experienced a Reduction in Transfusion Burden.

In the overall population, 42.1% (8 out of 19) achieved RS+.

In the subset, the rate is 35.3% (6 out of 17).

Non-RS (No Reduction in Transfusion Burden):

Non-RS represents patients without a reduction in transfusion burden.

In the overall population, 42.9% (3 out of 7) fall into the Non-RS category.

In the subset, the rate is higher at 60% (3 out of 5).

As we can see, the response was better in the HTB population for RS- patients, otherwise, rates of HI-E and TI were similar irrespective of transfusion burden or RS status. This indicates a broad spectrum activity of the molecule.

The second trial is an ongoing phase 2 trial of KER-050 as monotherapy or in combination with ruxolitinib in Anemia and Thrombocytopenia in patients with Myelofibrosis. Here, till April, data showed an increase of platelets and reticulocytes after treatment. The drug was generally well-tolerated.

Financials

KROS has a market cap of $1.29bn and a cash balance of $288mn. Research and development expenses were $34.1 million for the third quarter of 2023, while general and administrative expenses were $9.1 million. At that rate, they have a cash runway of some 6-7 quarters.

The stock has a very high institutional presence. keyholders are FMR, BlackRock, and Alkeon.

Bottomline

There are early indications of drug activity. However, Keros Therapeutics, Inc. needs to make an effort to put the data in context vis-à-vis rival therapies, approved or in the pipeline. I find the data interesting, however, I will wait for more competitive data before I make a call.