uniQure (NASDAQ:QURE) has made great progress to advance several of its gene therapy candidates in the recent year. Interim data was released from the phase I/II U.S. study of AMT-130 for the treatment of early-stage Huntington’s disease after 12 and 24 months of follow-up. There was a slight drop in the stock price due to the fact that a biomarker, known as Neurofilament Light Chain [NfL] saw a brief spike in the study. While a concern initially, this biomarker fell subsequently in all patients shortly thereafter. Other than that, treatment with AMT-130 was safe/tolerable.
There is a catalyst opportunity here, because another update is expected from this program. It is expected that uniQure will release updated data from both the U.S. and European phase I/II studies in Q4 of 2023. Besides this catalyst, there are a few other ones to look forward to before the end of 2023. At some point in the 2nd half of 2023, it is the company’s goal to initiate a phase 1/2 study of AMT-162 for the treatment of SOD-1 Amyotrophic lateral sclerosis [ALS]. Then, in Q4 of 2023, it intends to initiate a phase I/II study of AMT-260 for the treatment of patients with refractory temporal lobe epilepsy.
AMT-130 Program For Huntington’s Disease Advancing, Additional Data Update Expected
uniQure is developing its gene therapy candidate AMT-130 for the treatment of early-stage Huntington’s Disease. Several months ago, it released interim clinical data from its ongoing high-dose and low-dose cohorts from the U.S. phase I/II study. There was some data released showing that the gene therapy did well to help these Huntington’s Disease patients in relation to achieving benefits compared to natural history. Such an accomplishment was done in terms of several measures for this disorder, such as: Total Motor Score, Total Functional Capacity and the composite Unified Huntington’s Disease Rating Scale. AMT-130 was also able to show an improvement for these patients compared to a few biomarkers as well, with Neurofilament Ligh Chain [NfL] being one of them. Speaking of which, this biomarker is what caused the stock to drop after the news of the data was released. It was said that patients given AMT-130 saw a brief increase in cerebral spinal fluid Neurofilament Light Chain [NfL]. While this is definitely not a good thing, there are three points to consider here. The first is that such a spike in NfL reached a high at 1-month post dosing and then dropped off. Secondly, it was not dose dependent.
Thus, subsequent doses did not increase NfL. Third and last, all the patients experienced subsequent declines of CSF NfL, which removes the risk of neurodegeneration remaining. It remains to be seen what happen with the next interim update, but if there is another spike of CSF NfL shown again then this means there is a pattern of a brief spike of this biomarker in the first month of treatment. Hopefully, safety and efficacy data continue to warrant further evaluation. This a large market opportunity for this company and should it ultimately receive approval, then it would be a huge boost for the biotech and its shareholders. The Huntington’s disease treatment market size is expected to reach $2.93 billion by 2030. If the next update goes well for AMT-130, then uniQure intends to meet with both U.S. and European regulators to see if it can possibly advance a late-stage study, which may ultimately be used to seek for regulatory approval of AMT-130 for early-stage Huntington’s Disease.
Other Study Initiations To Provide Additional Shots On Goal
Data thus far for AMT-130 for early-stage Huntington’s Disease patients is not that bad, however, what remains to be seen is if there is a pattern of an increase of CSF NfL when a patient is given this gene therapy. My opinion is that a one-month transient spike increase of this biomarker is not bad. However, should the next interim update be worse, then that may put the program in jeopardy. The good thing about uniQure is that it is not only reliant on AMT-130. It has made several advancements with other gene therapies targeting other indications. The first of which would be the use of AMT-260 for the treatment of patients with refractory mesial temporal lobe epilepsy [MTLE]. It received clearance of the Investigational New Drug [IND] Application of AMT-260 to treat this patient population. Thus, it received clearance to initiate a phase I/IIa clinical trial for this program from the FDA. It is expected that the first patient for this study will be screened in Q4 of 2023.
Besides the use of AMT-260 for refractory MTLE being moved forward, there are two other catalyst opportunities for investors to look forward to. The first would be the initiation of a phase I/II clinical trial using AMT-162 for the treatment of patients with SOD1 Amyotrophic Lateral Sclerosis [ALS], which is expected to begin in the 2nd half of 2023. The Amyotrohphic Lateral Sclerosis market is expected to grow to $1.2 billion by 2027. However, being that only SOD1 ALS is being targeted this population would be smaller. Still, it is said that about 25% of ALS patients have the SOD 1 mutation. Another catalyst would be an IND submission of AMT-191 for the treatment of patients with Fabry Disease, which is expected to occur in the 2nd half of 2023. At the moment a toxicity study has been initiated in non-human primates. Should no toxicity issues be found, only then will an IND submission occur.
Financials
According to the 10-Q SEC filing, uniQure had cash, cash equivalents and investment securities of $628.6 million. One thing to note is that this cash on hand doesn’t include the additional $100 million which was received as a milestone payment from CSL Behring in July of 2023. This is one of the stronger biotechs in terms of cash position and the reason why I state that is because of its expected cash runway. it believes that it has enough cash on hand to fund its operations into Q2 of 2026. The earliest it might need to start looking into raising cash again would be in 2025. Other than that, it is in good shape financially.
Risks To Business
There are several risks that investors should be aware of before investing in uniQure. The first risk to consider would be with respect to the phase I/II study, which is using AMT-130 for the treatment of early-stage Huntington’s Disease patients. It is expected that additional results will be released from this study in Q4 of 2023. There is likely going to be another spike in CSF NfL noted again and this may be seen as a negative reaction by the market. This means even if every other data is shown to be good, then another spike in this biomarker could be a risk for this catalyst. However, I believe another brief one-month spike being shown would create a buying opportunity. As long as the CSF NfL doesn’t spike for an extended period of time over several months, then this program should be okay.
A second risk to consider would be whether or not the data shown at this next update warrants further advancement of AMT-130 for Huntington’s Disease. That’s because uniQure is expected to meet with U.S. and European regulators in Q1 of 2024 and there is no assurance that it will receive clearance to begin late-stage pivotal studies in either of these regions. The final risk to consider would be with the other gene therapies being advanced in the pipeline, which are AMT-260 and AMT-162 for the treatment of patients with refractory MTLE and SOD1 Amyotrophic Lateral Sclerosis respectively. Even with these studies being completed, there is no guarantee that one or both of these programs will obtain positive results.
Conclusion
uniQure had made great progress in advancing the use of AMT-130 for the treatment of patients with Huntington’s Disease. It is expected to provide another data update for this program in Q4 of 2023. Should this program ultimately be successful, then it would target a very large market opportunity. The Huntington’s disease treatment market size is expected to reach $2.93 billion by 2030. Just in case this program doesn’t work out, then it has other gene therapies in the pipeline which it is advancing, as I highlighted above. With progress made in advancing AMT-130 for early-stage Huntington’s Disease patients, plus several catalysts to look forward to in the coming months, I believe that investors might be able to capitalize on any potential gains made.
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