SYRS - Syros: Multiple Shots On Goal In Blood Cancer Space

Summary

• Final results from pivotal study SELECT-MDS-1, using Tamibarotene for the treatment of patients with newly diagnosed high-risk MDS that have RARA gene overexpression, expected Q3 of 2024.
• The global myelodysplastic syndrome market is expected to reach $5.6 billion by 2032; 50% of high-risk MDS patients have RARA expression.
• Initiation of phase 2 study known as SELECT-AML-1, using Tamibarotene for treatment of newly diagnosed AML patients who are RARA positive expected Q1 of 2023; Final results expected Q4 of 2023.
• Initiation or program update for phase 3 study using SY-2101 for the treatment of patients with newly diagnosed acute promyelocytic leukemia expected in the 2nd half of 2023.

Syros Pharmaceuticals ( SYRS ) is a great speculative biotech play to look into. The reason why I state that is because it has several shots on goal in using different drugs all of which target different cancer indications. I believe this offers a good opportunity, because it is already in late-stage development for many of these programs. For instance, it expects to release results from a late-stage study known as SELECT-MDS-1, which is using Tamibarotene for the treatment of patients with newly diagnosed high-risk myelodysplastic syndrome ((MDS)) that have RARA gene overexpression. This pivotal study is expected to have results released in Q3 of 2024. Just in case this pivotal study is not successful, it is also targeting another cancer patient population in an earlier mid-stage study. This involves a phase 2 study known as SELECT-AML-1, which is using Tamibarotene for the treatment of newly diagnosed Acute Myeloid Leukemia (AML) patients who are RARA positive. This study is expected to start in Q1 of 2023 and Syros anticipates that results from the phase 2 randomized portion will be available by Q4 of 2023. One key thing to note about both of these programs with tamibarotene is that this drug is being advanced for the treatment of these patient populations in combination with other already approved chemotherapy drugs. As you can see, these are just a few of the trials underway that are in late-stage clinical development. The biotech also hopes to initiate a phase 3 study using another drug known as SY-2101 in patients with newly diagnosed acute promyelocytic leukemia ((APL)) in the 2nd half of 2023. With a pretty diverse pipeline, I believe it may offer a good opportunity as a speculative biotech play.

Tamibarotene For The Treatment Of Patients With Newly Diagnosed High-Risk Myelodysplastic Syndrome

The first clinical program to go over involves the use of Tamibarotene for the treatment of patients with newly diagnosed High-Risk Myelodysplastic Syndrome. Myelodysplastic Syndrome ((MDS)) involves a group of cancers that keep your blood stem cells from maturing into healthy blood cells. However, MDS can also cause other problems as well ranging from developing Acute Myeloid Leukemia (AML) or anemia (lack of healthy red blood cells to carry oxygen), frequent infections and bleeding episodes which may not stop. Healthy red blood cells are made in the soft spongy area known as the bone marrow. If such production doesn't happen, then red blood cells die in the bone marrow. When red blood cells die in the bone marrow, there is no room for the healthy red blood cells to exist. This effect, leads to serious problems, which is why MDS needs to be taken care of. The global myelodysplastic syndrome market is expected to reach $5.6 billion by 2032 . There are several symptoms that these patients experience as well, which are as follows:

• You are tired/weak
• Skin becomes pale
• Bleed more often
• Frequent infections
• Frequent fevers

As I stated above, Syros isn't just going after a High-Risk Myelodysplastic Syndrome patient population, it is going after those who specifically have the genetic RARA mutation. Not to worry though, because it is still a pretty good sized population for it to go after. Consider that there are about 50% of high-risk MDS patients who have the RARA gene overexpression. Of course, this is being deployed for front-line therapy, not patients who are refractory or have gone through many other therapies already. Therefore, Tamibarotene is specifically being used to target a specific MDS patient population.

I believe this biotech has huge potential because it is currently running a pivotal study for this program. The phase 3 study it is currently running is known as SELECT-MDS-1 , which it is using Tamibarotene in combination with Azacitidine for the treatment of newly diagnosed high-risk myelodysplastic Syndrome (HR-MDS) patients with RARA gene overexpression. This study randomized approximately 190 patients 2:1 who were moved to either one of these dosing groups as follows:

• Tamibarotene + Azacitidine (Chemotherapy)
• Placebo + Azacitidine

The primary endpoint is looking to compare the complete response ((CR)) rate between the two dosing groups I described directly above. The secondary objectives were those in which you would normally see in a cancer study such as: Objective response rate ((ORR)), Event-free survival ((EFS)), overall-survival ((OS)), transfusion independence rate, time to and duration of initial and complete responses and safety as well. The key thing here being the complete response as the primary endpoint. This, in my opinion, is the most important program in the pipeline for Syros. Why do I say that? That's because it is the first of the company's pivotal studies which will report clinical data. Results from the phase 3 pivotal SELECT-MDS-1 study in newly diagnosed HR-MDS patients with RARA gene overexpression are expected to be released in Q4 of 2023 or Q1 of 2024. As long as the primary endpoint is met with statistical significance, then that opens a possible New Drug Application (NDA) to the FDA of Tamibarotene + Azacitidine for the treatment of these HR-MDS patients with the RARA gene overexpression. Such a filing could possibly happen in 2024.

Financials

According to the 10-Q SEC Filing , Syros Pharmaceuticals had cash, cash equivalents and marketable securities of $244.5 million as of September 30, 2022. The reason for the cash on hand is because Syros announced that it would acquire Tyme Technologies . This gave it Tyme's pipeline plus the cash it already had. Not only that, but at the very same time Syros had announced an oversubscribed $130 million private investing in public equity (PIPE) financing at a price per unit of $0.94. This was led by multiple institutions, but it's nice to see that it was able to raise cash with this merger. This cash will help to fund its operations for quite some time. Matter of fact, the estimate is that the current cash on hand will be enough to fund its operations into 2025. This means, should it need to raise cash, it may not need to do so until the beginning of 2024. The only way a cash raise might be done earlier is if it releases positive results from the phase 2 SELECT-AML-1 study. If that happens, with the stock trading much higher, than I expect a cash raise to happen immediately thereafter.

Risks To Business

There are several risks that traders/investors should be aware of before investing in Syros Pharmaceuticals. The first risk to consider would be with respect to the ongoing phase 3 study known as SELECT-MDS-1, which is using Tamibarotene for the treatment of patients with newly diagnosed high-risk myelodysplastic syndrome ((MDS)) who have RARA gene overexpression. Results from this late-stage study are expected to be released by Q3 of 2024. There is no guarantee that this trial will meet on the primary endpoint once the final data is released. The second risk to consider is with respect to the phase 2 study known as SELECT-AML-1, which is using Tamibarotene in combination with venetoclax and azacitidine in newly diagnosed unfit AML patients who have RARA overexpression. The randomized phase 2 portion of the study is expected to begin in Q1 of 2023 and from there data from it is expected to be released in Q4 of 2023. While Tamibarotene is being deployed as a triplet with venetoclax and azacitidine, there is no guarantee that it can do better in treating this patient population compared to the doublet combination of venetoclax and azacitidine. The final risk to consider would be with respect to the use of SY-2101 for the treatment of newly diagnosed acute promyelocytic leukemia patients. It is anticipated that a phase 3 study will be initiated in the latter part of this year, but management is expected to provide an update for this program in the 2nd half of 2023. As such, there is no guarantee that a late-stage study will be initiated for this specific program.

Conclusion

The final conclusion is that Syros Pharmaceuticals is a great speculative biotech play to look into. The reason why I state that is because it has several late-stage programs in place to rely on. While there is no guarantee that any or all will be successful, it is nice to see that it has a diverse pipeline. As far as 2023 goes, there are a few catalysts which traders/investors can look forward to. One would be the initiation of the phase 3 study, using SY-2101 for the treatment of patients with newly diagnosed acute promyelocytic leukemia, which is expected in the 2nd half of 2023. The other catalysts would be the initiation of the phase 2 SELECT-AML-1 study in Q1 of 2023 and then results from it to be released in Q4 of 2023. With a diverse pipeline going after several types of hematological malignancies, plus a few catalysts expected in 2023, these are the reasons why I believe it is a great speculative biotech play to look into.

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