GERN - Seeking Alpha article
Geron: FDA PDUFA Review With Continued Imetelstat Advancement
May 01, 2024 4:23 PM ETGeron Corporation (GERN) StockGERNW6 Comments
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Terry Chrisomalis
Investing Group Leader
Summary
Geron Corporation has a PDUFA date of June 16th of 2024 for the FDA to decide upon whether imetelstat should be approved for patients with low-risk myelodysplastic syndrome.
The FDA Oncologic Drugs Advisory Committee already voted in favor of imetelstat 12 to 2 for patients with low-risk myelodysplastic syndrome.
The European Commission has already accepted the MAA for review of imetelstat for low-risk myelodysplastic syndrome; European approval is possible in 2025.
Imetelstat is also being evaluated in the ongoing phase 3 IMpactMF study for the treatment of patients of relapsed/refractory MF; Interim analysis expected in the 1st half of 2025 and final data expected in the 1st half of 2026.
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Jacob Wackerhausen
Geron Corporation (NASDAQ:GERN) is gearing up for a major milestone as a biotech company. It has a PDUFA date set for June 16th of 2024, which is the date by which the FDA will decide whether imetelstat should be approved for the treatment of patients with low-risk myelodysplastic syndrome [LR-MDS]. These are patients who have failed to respond, lost response to or ineligible for Erythropoiesis-stimulating agents [ESAs]. An FDA advisory panel already voted in favor of imetelstat for this LR-MDS patient population, recommending that the risk-benefit profile is ideal for regulatory approval of it.
The FDA still has to approve it based on this recommendation. However, with such a recommendation, I don't see how the FDA could reject approval. This regulatory approval is only going to be based on its ability to market this drug in the United States only.
It is already in the process of having imetelstat reviewed for the same patient population for Europe. That is, the European Commission [EC] is already in the process of reviewing it for possible approval for all the European territories as well. Should the review go well, then it is expected that this drug could possibly be approved for these territories in 2025. Lastly, the goal is to advance imetelstat for multiple indications. As such, it is also running another phase 3 study as part of its pipeline known as IMpactMF, which is using imetelstat for the treatment of patients with relapsed/refractory Myelofibrosis [MF] or r/r MF. An interim analysis from this trial is expected in the 1st half of 2025 and from there, a final analysis from this late-stage study is expected in the first half of 2026.
FDA Review Date Catalyst Rapidly Approaching For Imetelstat
The main program in Geron's pipeline would be the use of imetelstat for the treatment of patients with low-risk myelodysplastic syndrome [LR-MDS]. These are patients who do not even respond to standard of care [SOC] Erythropoiesis-stimulating agents [ESAs]. The potential here is massive because it has already gone on to accomplish several items to potentially obtain FDA approval of imetelstat for the treatment of this patient population. Matter of fact, everything seems to be lining up perfectly thus far. The only hurdle left now would be the actual FDA review date that has been set up. This is a PDUFA date of June 16th of 2024, where the agency will decide whether imetelstat should be approved for the treatment of these patients with LR-MDS. Myelodysplastic Syndrome [MDS] is a type of blood disorder characterized as the spongy material inside the bones not working properly. In turn, it cannot produce red blood cells [RBCs] in an adequate fashion for these patients. Some symptoms that these patients experience are as follows:
Shortness of breath
Fatigue
Pale skin color due to anemia
Unusual types of bruising occurring.
The global Myelodysplastic Syndrome market is expected to reach $6.63 billion by 2030. However, in the case of Geron, it is specifically going after low-risk Myelodysplastic Syndrome patients. This is a huge population to go after still, even if it were only to target this subpopulation.
What makes me say that? Well, it is said that approximately 68% of patients remain in the low-risk category. Plus, there is another highly important item to note, which is that the patients being targeted are an unmet need. These are low-risk MDS patients who have failed to respond, stop responding to, or ineligible to receive SOC Erythropoiesis-stimulating agents [ESAs]. What are these ESAs, and how do they help these patients? In essence, what they do is stimulate the bone marrow to produce more RBCs than a patient needs. In addition, it is also used to greatly reduce the number of blood transfusions being done.
The real question is, why should investors look into this upcoming PDUFA date of imetelstat for the treatment of these LR-MDS patients? As with all regulatory drug approvals, nothing is guaranteed. However, in this case, I believe that there is a good chance that it be approved to treat this specific patient population. The basis of this statement is because of the highly positive vote that was obtained from the FDA advisory panel. That is, the FDA Oncologic Drugs Advisory Committee voted 12 to 2 in favor of recommending approval of imetelstat. This is highly positive, and I believe there is a good chance that it will be approved. However, it is ultimately up to the FDA and there is always a chance that it may end up rejecting U.S. marketing approval. It's important to keep in mind that the FDA uses these panels as recommendations, but ultimately doesn't have to follow them.
Besides the positive vote, I believe there is another excellent reason on why FDA approval is almost guaranteed. It is because of the primary endpoint being met in the phase 3 IMerge study. This study recruited such low-risk MDS patients and was testing the use of imetelstat compared to placebo because of transfusion independence over a consecutive 8-week period for 12 months. Most MDS patients have a need for transfusions to be able to stimulate their blood cells; thus, the primary endpoint was to achieve red blood cell transfusion independence [RBC-TI] over this period. It was shown that RBC-TI was superior in the imetelstat treatment group compared to the placebo treated group. As such, treatment with the drug was statistically significant compared to placebo, with a p-value of p<0.001.
If it were only the FDA PDUFA date approaching as a milestone in terms of regulatory approval, that would be one thing, but there might be another territory that it could receive approval of imetelstat for. This would be regarding an already submitted Marketing Authorization Application [MAA] of this drug for the treatment of this patient population to the European Commission [EC]. If the review for this territory goes well, then Geron can possibly also receive marketing approval of imetelstat for LR-MDS patients in the European territories in 2025 as well.
Possible Expansion Opportunity Of Imetelstat Can Lead To Another Catalyst
The thing is that while the PDUFA date is a near-term catalyst that Geron has, that doesn't mean that it is not working on expanding the use of imetelstat towards the treatment of other hematological malignancy [blood cancer] patient populations. The reason why this is possible is because of telomerase inhibition, whereby telomerase is no longer in place. Without telomerase being in place, this leads to cells becoming shorter upon division and eventually dying off [apoptosis].
To see if Geron can advance the use of imetelstat for another blood disorder, it has initiated a phase 3 study known as IMpactMF. This particular late-stage study is using this drug to treat patients with relapsed/refractory myelofibrosis [MF]. That is, to recruit intermediate-2 to high-risk MF patients who relapse after Janus associated kinase [JAK] inhibitor treatment. Myelofibrosis [MF] is characterized as a rare bone marrow cancer where scarring occurs, thus leading to a lower than expected production of red blood cells [RBCs].
This low amount of blood cells leads to anemia [low blood cell count], which leads to weakness or fatigue. The global Myelofibrosis market size is projected to reach $2.89 billion by 2031. However, Geron believes that between the United States and Europe for the targeting of relapsed/refractory MF patients, it could target a >$3.5 billion market opportunity.
How is it even possible for imetelstat to help these r/r MF patients? That's because of how dire this patient population is. Especially, when you find out that a large majority of them fail when taking JAK inhibitors. It is noted that there is a discontinuation rate of 75% after 5 years with this treatment option. Thus, a drug like imetelstat could be given instead to patients that might improve their response. Having said that, this IMpactMF phase 3 study, is a first of its kind trial deploying overall survival [OS] as the primary endpoint for this specific study.
The reason why I brought up this program is that in the early part of next year, there is a major milestone expected for it. It is expected that an interim analysis from this phase 3 IMpactMF study will be released in the 1st half of 2025. From there, a full final analysis from this late-stage registrational trial is expected to be released in the 1st half of 2026.
Financials
According to the 10-K SEC Filing, Geron Corporation had cash, cash equivalents and marketable securities of $378.1 million as of December 31, 2023. The reason for the cash on hand is because of several financial transactions it enacted in 2023. It received about $213.3 million from an underwritten public offering of common stock and pre-funded warrants in January 2023.
In addition, it received $105.9 million from the exercise of outstanding warrants and $29.7 million in net proceeds drawn down from a Loan Agreement with Hercules and SVB. It believed that this would be enough cash to fund its operations into Q3 of 2025. However, it also has to account for the funds it will need to prepare for possible commercialization of imetelstat for LR-MDS. As such, it enacted a huge cash raise with the pricing of an underwritten offering. With this offering, it raised approximately $150 million in gross proceeds.
With the cash on hand, plus the gross proceeds raised from this recent offering, this should extend Geron Corporation's cash runway into the early part of 2026. Its cash burn is about $394.6 million per year.
Risks To Business
There are several risks that investors should be aware of before investing in Geron. The first risk to consider would be regarding the upcoming PDUFA date of June 16th of 2024, where the FDA will decide if imetelstat should be approved for the treatment of patients with low-risk myelodysplastic syndrome [LR-MDS]. Even though the advisory FDA panel voted in favor of recommending imetelstat for the treatment of this patient population, there is no assurance that U.S. marketing approval will be achieved. As I stated above, the FDA only takes the recommendation of the advisor panel, but it doesn't have to abide by it.
A second risk to consider would be regarding the ongoing review by the European Commission [EC] of imetelstat for the treatment of patients with low-risk myelodysplastic syndrome. Even though the regulatory application was accepted for review, there is no guarantee that the drug will be approved for the treatment of this patient population in the European territories.
The third and final risk to consider would be regarding the possible expansion opportunity of imetelstat I described above. This would be regarding the ongoing phase 3 IMpactMF study, which is using this drug for the treatment of patients with relapsed/refractory MF. An interim analysis from this late-stage trial is expected to happen in the early part of 2025 and there is no assurance that positive results will be achieved for it. Nor, that there will be a positive outcome when the final analysis is revealed in 2026.
Conclusion
Geron Corporation is gearing up to have a huge inflection point for investors to keep an eye on. This would be regarding the PDUFA review date of June 16th of 2024 of imetelstat for the treatment of patients with transfusion-dependent [TD] anemia in adult patients with LR-MDS who have not responded to or lost response to or are ineligible for erythropoiesis stimulating agents [ESAs]. This possible regulatory approval for this drug is only the beginning because there is an ongoing review by the European Commission for the European territories.
I believe that the last point to make is that telomerase expression is observed in about 90% of biopsies taking in various types of cancer. As such, it has already advanced its pipeline towards the use of imetelstat for the targeting of front-line MF patients [IMproveMF] and for the targeting of relapsed/refractory acute myeloid leukemia and high-risk MDS patients [IMpress]. There is no assurance that the drug will work out for either of these other hematological malignancies, but they do provide additional shots on goal for the pipeline.
Editor's Note: This article discusses one or more securities that do not trade on a major U.S. exchange. Please be aware of the risks associated with these stocks.
This article was written by
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Terry Chrisomalis
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Terry Chrisomalis is a private investor in the Biotech sector with years of experience utilizing his Applied Science background to generate long term value from Healthcare.
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