Geron’s Data Allows Development Of Several Catalysts (GERN)

Geron Corporation (NASDAQ:GERN) is a great speculative biotech play to look into. The reason why I state that is because it just recently reported positive results from its phase 3 study using its lead drug known as imetelstat for the treatment of patients with myelodysplastic syndrome (MDS). Not only did it obtain the primary endpoint from its phase 3 clinical study known as IMerge, but it also went on to achieve statistical significance with respect to the secondary endpoint as well.

While there have been substantial gains in Geron Corporation share price based off of this data, I believe that there is room for it to go higher. Why do I make this claim? Well, it is because by meeting the primary endpoint of transfusion independence with statistical significance, it opens up several catalysts which I believe could allow the stock to trade higher. The first catalyst which I believe could allow the stock to trade higher would be the submission of a New Drug Application (NDA) to the FDA of imetelstat for the treatment of patients with myelodysplastic syndrome (MDS) in 2023. From there, there also is the submission of the application of this drug for the treatment of this patient population to the European Union (EU) also in 2023. Lastly, if these regulatory reviews go well, then another catalyst in play would be the commercial launch of imetelstat for MDS in 2024.

Another reason why I think there is room for Geron Corporation to grow after recent stock gains is because despite the rise in the stock price by 40%, there is the proof of concept established with this drug for this patient population. It has another ongoing phase 3 study known as IMpactMF, which is exploring imetelstat for the treatment of patients with refractory myelofibrosis (MF). Interim results from this study could be released by 2024, and that could provide another boost in shareholder value. Furthermore, Geron is looking to see if imetelstat can be used in combination with ruxolitinib in patients with frontline myelofibrosis. Should synergy be observed here, then this is another avenue of expansion for imetelstat. Based on the completion of a phase 3 study establishing proof of concept with its lead drug, plus the presentation of so many catalysts on the way, these are the reasons why I believe that Geron is a great speculative biotech play to look into.

IMerge Phase 3 Results Sets Up Multiple Catalyst Opportunities

Geron announced positive results from its phase 3 IMerge study, using its main drug imetelstat for the treatment of patients with myelodysplastic syndrome (MDS). More specifically, this late-stage trial recruited a total of 170 transfusion-dependent patients with Low or Intermediate-1 risk MDS. One key reason why I believe these study results are outstanding is because these are patients who have relapsed or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA).

In essence, ESAs are medications that Doctors use on MDS patients in an attempt to stimulate the bone marrow to produce red blood cells for the patient. In this particular case, these patients fail to have their bone marrow produce essential red blood cells despite receiving such medication. Having said that, imetelstat was able to help these patients in a statistically significant manner. The primary endpoint of this phase 3 study was the rate of red blood cell (RBC) transfusion independence (TI) for any consecutive period of 8 weeks or more, or 8 week RBC-TI rate. The reason why this trial was met with statistical significance is because it was shown that 40% of the 118 patients who received imetelstat achieved TI at 8 weeks, compared to placebo which only had 15% of the 60 patients achieving TI at 8 weeks. Thus, the drug achieved statistical significance over placebo with a p-value of <0.001.

This is important, because in order for Geron to seek regulatory approval, it needed to meet this endpoint. However, why I believe it has a great shot at being approved in U.S. and Europe is because it went beyond what was needed. What do I mean by that? Well, it also met the secondary endpoint with statistical significance. The secondary endpoint is normally placed as an exploratory endpoint and not needed for regulatory approval. Regardless, the biotech was able to achieve this measure as well. The secondary endpoint was transfusion independence (TI) at week 24. With regards to this measure, it was shown that about 28% of imetelstat treated patients achieve TI at 24 weeks, compared to 3.3% of placebo treated patients of TI at 24 weeks.

Again, as I stated above, this creates multiple catalyst opportunities for this company. It anticipates that it will file a New Drug Application (NDA) to the FDA in mid-2023, which will be a huge major catalyst for investors to look forward too. A second major catalyst from there would be the submission of a marketing authorization application (MAA) to the European Medicines Agency (EMA) in the 2nd half of 2023. These are just the submissions of the applications only. If all goes well with the review of both of these applications, then the granting of regulatory approvals and subsequent commercial launches in 2024 would be considered as additional catalysts/inflection points to look forward too.

Proof Of Concept Established For Imetelstat Brings About Hope For Next Late-Stage Data Readout

While the catalyst with respect to the data readout of the phase 3 IMerge study is finished, it did accomplish something else. It proved that imetelstat can be used towards hematological malignancies. This opens up the door for another late-stage study data readout. Specifically, the use of this drug is being explored in the ongoing phase 3 IMpactMF study. The goal of this particular study is to target myelofibrosis (MF) who are relapsed/refractory to a treatment with a janus associated kinase (JAK) inhibitor. It is said that about 320 patients with intermediate-2 or High-risk MF patients who are relapsed or refractory to such JAK inhibitor therapies, will be randomized 2:1 to either receive imetelstat or Best Available Therapy (BAT). Best Available Therapy meaning another drug/treatment given to treat this disease, however, it can’t be a JAK inhibitor.

Myelofibrosis is a rare type of bone marrow cancer that disrupts the body’s normal production of blood cells. What happens is that it causes scarring in the bone marrow and, with that, leads to several other associated problems. Such problems are: Severe anemia leading to fatigue, lower number of blood-clotting cells (platelets) increasing the risk of bleeding, and enlarged spleen. Another thing to note is that there are two ways it can develop. This broken down into:

• Primary myelofibrosis – myelofibrosis that just occurs on its own
• Secondary myelofibrosis – myelofibrosis which develops from another bone marrow disorder.

The thing is that there are two JAK inhibitors which have been approved to treat patients with intermediate-risk and high-risk myelofibrosis (MF). They are ruxolitinib and fedratinib. While they have been shown to work well in increasing several measures for this patient population, but there is a downside. The downside being that a lot of patients don’t end up benefiting from them, because of discontinuation due to adverse events or not responding to the treatment.

After discontinuing treatment with ruxolitinib for instance, survival durations range from 11 to 16 months in several studies. What is imetelstat then going to do? It is being given as a single agent therapy after patients have become relapsed/refractory (don’t respond) to JAK inhibitors like ruxolitinib. Why bring up this late-stage IMpactMF study? The reason why I bring it up is because there is a catalyst that traders/investors can look forward too. It is expected that an interim analysis from this phase 3 IMpactMF study using imetelstat for the treatment of relapsed/refractory MF patients will be released in 2024. Being that Geron’s drug established proof of concept in treating patients with MDS, there is a high probability it may do well in this other hematological malignancy patient population. This doesn’t guarantee success, though, but still it is nice to see that its drug was capable of meeting the primary endpoint in a late-stage phase 3 study.

Also, what I described above is one avenue to target the MF population, which was relapse/refractory MF patients. There is an ongoing phase 1 study known as IMproveMF, which is using imetelstat in combination with ruxolitinib in front-line MF patients. Results from this study are expected by the end of 2023. As you can see, there are two shots on goal in this MF population. One phase 3 study using imetelstat alone against a relapsed/refractory MF population and then a phase 1 study using imetelstat in combination with ruxolitinib in 1st-line MF patient population.

Financials

According to the 10-Q SEC Filing, Geron Corporation had $195 million in cash and marketable securities. It also had noted up to $121 million it could obtain from the exercise of the currently outstanding warrants and up to $50 million from the current debt facility it has in place. It believed that all of this would be enough to fund its operations into mid-2024.

The thing is that after it reported positive results from the phase 3 IMerge trial, it chose to raise cash immediately. It enacted an underwritten public offering of 55,876,297 shares of its common stock at a public offering price of $2.45 per share and pre-funded warrants to purchase 25,000,000 shares of its common stock. The pre-funded warrants are being sold at a public offering price of $2.449 per pre-funded warrant. In addition, Geron granted the underwriters a 30-day option to purchase up to an additional 12,131,444 shares of its common stock. The offering is expected to close on or about January 10, 2023 and is expected to bring in about $198.1 million before deducting expenses.

Risks To Business

There are several risks that traders/investors should be aware of before investing in this biotech. The first risk to consider would be with respect to the recent positive results from the phase 3 IMerge study. While it is expected to file regulatory applications to the U.S. and Europe for imetelstat for MDS in the 1st half of 2023, there is no guarantee that it will obtain marketing approval for one or either of these territories.

Another risk to consider would be with respect to the release of results from the IMproveMF phase 1 study, which is using imetelstat in combination with ruxolitinib for the treatment of patients in front-line MF patients. Results from this early-stage study are expected by the end of 2023 and there is no guarantee that it will be successful.

The final risk involves the release of results from the other ongoing phase 3 study which the company is running, known as IMpactMF. An interim analysis from this late-stage study is expected to be released by 2024. If the first analysis of this study is not good, then it is possible that it could be cancelled. Not only that, but Geron would lose the ability to branch out the use of imetelstat towards another patient population.

Conclusion

The final conclusion is that Geron Corporation is a great speculative biotech play to look into. As I stated above, it didn’t only establish statistical significance with respect to the primary endpoint of 8-week transfusion independence (TI), but also the secondary endpoint of 24-week TI. With its successful phase 3 study, it is ready to move on towards filing regulatory submissions of imetelstat for lower-risk MDS for U.S. and Europe in 2023. This sets up the potential launch of this drug for this indication in 2024, of course, if it ultimately receives regulatory approval for these territories.

There is another potential opportunity for investors to look forward to, especially as it relates to another late-stage clinical trial. Interim results from the phase 3 IMpactMF study, using imetelstat for the treatment of patients with relapsed/refractory myelofibrosis, are expected in 2024. If these interim results are positive, then it would solidify another win for the company. With a successful outcome of the phase 3 IMerge study, plus regulatory submissions of imetelstat for MDS expected in 2023, these are the reasons why I believe Geron Corporation is a great speculative biotech play to look into.