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Silence Therapeutics (NASDAQ:SLN) is gearing up to report topline 36-week data from its phase 2 ALPACAR-360 study, which is using its drug zerlasiran [formerly known as SLN360] for the treatment of patients with high lipoprotein[a] and stable atherosclerotic cardiovascular disease [ASCVD]. It is expected to release such data in Q1 of 2024 and positive data here would reconfirm prior findings from a phase 1 study, whereby positive data was achieved. The hope is that positive data is achieved with respect to this phase 2 ALPACAR-360 study. Besides positive data causing the stock price to trade higher, it would also allow for several other catalysts to come about that could provide additional upside. Matter of fact, should results using zerlasiran for this ASCVD patient population be good, then it would mean another four catalysts on the way.
This is only with respect to just this program using this drug to target this patient population. Silence Therapeutics has several other programs in place that it is advancing in its pipeline using messenger RNA [mRNA] therapeutics. For example, there is another drug in its pipeline it is working on known as divesiran [formerly known as SLN124]. This clinical candidate is being advanced in the phase 1/2 SANRECO study for the treatment of patients with polycythemia vera [PV]. The importance of tracking this study is because it is also going to have data released in the coming months. It is expected that results from this study using divesiran to treat this patient population will be released in mid-2024. It is also in a good position with its cash on hand because it was able to receive cash through a few financial transactions.
Zerlasiran For The Treatment Of Patients With Cardiovascular Disease
One very important program to go over in the pipeline would be the use of zerlasiran, which is being developed to treat patients with cardiovascular disease. In particular, this clinical candidate is currently being explored in the phase 2 ALPACAR-360 study. The main thing for this drug is to be able to silence a gene that is responsible for creating the Lp[a] protein. By silencing this gene, it is expected to reduce the amount of this type of protein from roaming around in the patient’s body. In turn, this should then lead to reduced risk of patients developing other disorders like: Heart Attack, ischemic stroke, heart failure and other cardiovascular events. Cardiovascular disease can be referred to as a disorder with multiple conditions, which is the leadup to what I just noted, like heart attack or stroke. The global cardiovascular disease drugs market size is expected to reach $186.1 billion by 2032. One major component that occurs in cardiovascular disease would be the buildup of plaque on the walls of arteries, which narrows the blood vessels. This phenomenon is known as atherosclerotic cardiovascular disease [ASCVD]. When this happens, patients have suffered a host issue that I just noted. The goal is to reduce the Lp[a] gene, and that is done with zerlasiran. Patients are only given a one-time dose of zerlasiran to reduce this specific gene, however, at the same time, not permanently altering the DNA present. That is, to not permanently alter the gene and having the ability to be reversed if necessary. This is made possible by the mRNAi Gold Platform, which uses RNA interference [RNAi] to deliver small interfering RNAs [siRNAs] to silence disease genes without permanent alteration being necessary. Even better, this technology deploys a much better way to deliver such siRNAs, which is with the use of the GalNAc delivery technology. GalNAc is a naturally occurring sugar molecule that tells the siRNA what to exactly silence in the liver, thus having better selectivity over other RNAi molecules.
The use of zerlasiran is being explored in the phase 2 ALPACAR-360 study, which is targeting patients with high lipoprotein [a] and stable atherosclerotic cardiovascular disease [ASCVD]. This mid-stage study is continuing to recruit patients at the moment who are to either be given two dose levels of zerlasiran or placebo comparator. The placebo given as part of this study is sodium chloride. The primary endpoint of this study is to evaluate the change in Lp[a] from baseline of drug compared to placebo over a 36-week period. Again, this goes back to what I noted above in that the target goal of this drug is to reduce as much of the Lp[a] as possible. I believe it is important to look at the prospects of this company mainly for the fact that it is gearing up to report topline 36-week data from this phase 2 ALPACAR-360 study in Q1 of 2024. Should the data to be released from this study turn out to be good, then this would set up several other catalysts this year. Such catalysts are:
- Topline 48-week data from the phase 2 ALPACAR-360 study Q2 of 2024
- Present ALPACAR-360 data at a medical conference Q3 of 2024
- Present 60-week data from the phase 2 ALPACAR-360 study Q4 of 2024
If that wasn’t enough, this particular program has one additional catalyst to be released, which is multi-dose data from the phase 1 APOLLO study. This early-stage study was the basis for advancing zerlasiran for the treatment of patients with high lipoprotein[a] levels and stable ASCVD. Why is that? That’s because positive topline data released from this trial showed that there was a durable reduction in Lp[a] of up to 99%. Not only that, but such lipoprotein[a] levels remained 90% lower from baseline at study endpoint. This shows that the drug continued to work despite patients only having received one dose of zerlasiran. In terms of safety, there were no concerns found and the drug was said to be well tolerated. Speaking of the phase 1 multi-dose APOLLO study, it is expected that a presentation of results will occur in Q2 of 2024. This presents another catalyst for investors to look forward to.
Financials
According to the 6-K SEC Filing, Silence Therapeutics had $63.6 million of cash and cash equivalents and U.S. Treasury Bills as of September 30th of 2023. It was able to raise some cash during this particular quarter, which was approximately $15.2 million of net proceeds. It believed that it would have enough cash on hand to fund its operations for at least into Q1 of 2025. However, it has been able to add to its cash position through a private placement of 5,714,286 ADS shares at a purchase price of $21 per share per ADS. It raised approximately $120 million before expenses. This biotech is in good shape anyways, because of the potential with its mRNAi Gold Platform.
This is because it has several pharmaceutical companies that have already wanted to get their hands on using this particular technology. Such partnerships already established by Silence are with AstraZeneca (AZN), Mallinckrodt, and Hansoh Pharmaceutical (OTCPK:HNSPF). If all these deals workout, then it is expected that Silence Therapeutics could earn up to $5.5 billion in milestone payments plus royalties. For instance, just today February 23rd 2024, it received a $10 million milestone payment based on AstraZeneca advancing the first siRNA clinical candidate as part of the collaboration agreement made with both companies.
Risks To Business
There are several risks that investors should be aware of before investing in Silence Therapeutics. The first risk to consider is with respect to the advancement of zerlasiran, which is being advanced in the phase 2 ALPACAR-360 study targeting patients with high Lp[a] levels with stable ASCVD. There is no assurance that the 36-week topline data to be released from this study are going to turn out to be positive. Not only that, the hope is that it can advance this particular program towards phase 3 clinical testing. Should the data turn out to be bad, then not only will it be allowed to initiate a late-stage study, but this program may be ultimately terminated entirely.
The second risk to consider would be with respect to the advancement of the phase 1 SANRECO PV study, which is using divesiran for the treatment of patients with polycythemia vera [PV]. The hope is that the mRNAi Gold technology is able to have the ability to treat patients with PV, but it is not guaranteed to do so. I would like to believe that as long as it does well with zerlasiran for the treatment of patients with ASCVD, then that alone should be enough to carry it forward as good long-term biotech. Why is that? That’s because cholesterol drugs like Lipitor, Crestor and Zocor have been able to generate >$30 billion in sales. However, they target high cholesterol levels for cardiovascular disease, which can be modified with diet and exercise. On the flip side, there is an open market for a drug like zerlasiran, which targets high Lp[a] for cardiovascular disease. High levels of Lp[a] is a genetic risk factor that is not yet suitably targeted by current treatment options [no indicated treatments] targeting Lp[a] levels > or = to 50 mg/dL.
The third risk to consider would be with respect to the collaboration agreements I noted above with AstraZeneca and others. Even though it appears as though these programs are on good footing, with Silence having received a $10 million milestone payment from AstraZeneca for the first phase 1 study, there is no guarantee that positive results will be released from it. In addition, there is no way of knowing whether or not this or any other collaboration will ultimately result in a product being marketed by any of these big pharmaceutical companies. If one or any of these collaboration agreements falls by the wayside, then it means that Silence Therapeutics will not be able to receive the up to $5.5 billion in milestone payments.
Conclusion
Silence Therapeutics is gearing up to report several results in 2024. This would be with respect to the advancement of zerlasiran for the treatment of patients with high levels of Lp[a] with atherosclerotic cardiovascular disease [ASCVD] and divesiran for the treatment of patients with polycythemia vera [PV]. Both programs can offer investors with significant share price appreciation, but I believe the more important clinical drug to keep an eye on would be zerlasiran for ASCVD. The reason why I say this is because there is potential to tap into the untreated risk factor of Lp[a]. Thus, should the 36-week results to be released from the phase 2 ALPACAR-360 study turn out to be positive, then I believe the value of this biotech should rise significantly.
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