2023-06-23 12:32:02 ET
Summary
- The new drug application submission of mavorixafor for the treatment of patients with WHIM syndrome is expected in the 2nd half of 2023.
- Results from an ongoing phase 2 study using mavorixafor for idiopathic, cyclic, or congenital chronic neutropenia are expected to be released in Q2 or Q3 of 2023.
- A regulatory update on whether it can begin a phase 3 study using mavorixafor for idiopathic, cyclic, or congenital chronic neutropenia is expected Q2 or Q3 of 2023.
- Mavorixafor is an oral drug option that could be more safe/tolerable over existing approved therapies.
X4 Pharmaceuticals (XFOR) is a good speculative biotech play to look into. The reason I state that is because it has already reported positive results from a phase 3 study using its drug mavorixafor for the treatment of patients with WHIM (Warts, Hypogammaglobulinemia, Infections and MyeloKathexis) Syndrome. Having said that, there is a major catalyst approaching that investors could capitalize on. It is preparing to file a new drug application ("NDA") to the FDA of mavorixafor for the treatment of this patient population in the second half of 2023. The company already held a pre-NDA meeting with the FDA and it is the reason why it will be able to file a regulatory application to the FDA for use of mavorixafor for the treatment of this patient population. Still, the company was able to generate very impressive efficacy data when it comes to using this CXCR4 antagonist drug to treat patients with WHIM syndrome.
This is not the only regulatory update which is a must watch for traders and investors either. Another regulatory guidance update is to be released in the coming months: in Q2 or Q3 of 2023, it is expected that X4 Pharmaceuticals will provide an update on the use of mavorixafor for the treatment of patients with certain chronic neutropenic disorders. Specifically, whether or not the FDA will allow it to initiate a phase 3 study for this specific program. This regulatory update is possible, because it has already established phase 1b study data showing that one dose of this drug was able to increase and normalize neutrophil counts in patients with idiopathic, cyclic, or congenital chronic neutropenia. This was achieved either alone with mavorixafor monotherapy or concurrently with injectable granulocyte colony-stimulating factor ("G-CSF"). This study has already been expanded to a phase 2 one as well, to test out long-term use of this drug for this patient population. With an NDA of mavorixafor for the treatment of WHIM syndrome expected in the 2nd half of 2023, plus the potential of advancing another phase 3 study of mavorixafor in patients with certain chronic neutropenic disorders, these are the reasons why I believe that X4 Pharmaceuticals is a good speculative biotech play to look into.
NDA In 2nd Half Of 2023 Makes For A Good Trade Opportunity
As I stated above, X4 Pharmaceuticals is preparing to file an NDA in the second half of 2023. It was already able to hold a pre-NDA meeting with the FDA to file a regulatory application for this drug to the FDA. The most important reason on why it will be able to file its NDA of mavorixafor for the treatment of this patient population is because of the positive results it achieved in the 4WHIM phase 3 study . Before diving into the data, it is important to understand what WHIM Syndrome is. WHIM Syndrome occurs as a result of an inherited immune deficiency characterized by neutropenia, B cell lymphopenia, myelokathexis, hypogammaglobulinemia and recurrent infections. WHIM takes its name because of the symptoms spelled out as: Warts, Hypogammaglobulinemia, Infections, and Myelokathexis. The problem is that not all people with WHIM Syndrome have all 4 signs and symptoms of this disease, which it makes it difficult to diagnose.
Positive results were achieved in the 4WHIM phase 3 study , which was a double-blind, randomized, placebo-controlled study which recruited a total of 31 WHIM syndrome patients who were the age of 12 and over. Patients were either given 400 mg of mavorixafor or placebo for a total of 52 weeks. This trial was able to meet on the primary endpoint and the first key secondary endpoint as well. With respect to the primary endpoint it was noted that treatment with mavorixafor achieved statistically significant TAT-ANC over placebo. TAT-ANC was measuring the length of time that patients' absolute neutrophil counts [ANC] remained above a clinically meaningful threshold of 500 cells per microliter over a 24-hour period at 4 time points through the entire 52-week study. Why is it important to track the ANC for these patients with WHIM syndrome? It is because the lower a patient's neutrophil count is, the higher the risk there is of them getting an infection.
Thus, why this measure was used as part of the primary endpoint for this 4WHIM phase 3 study. X4 Pharmaceuticals' drug mavorixafor was able to achieve this primary endpoint with statistical significance compared to placebo as shown directly below:
- Mean [Average] TAT-ANC was 15.04 hours for those on mavorixafor
- Mean TAT-ANC was 2.75 hours for those on placebo
Mavorixafor achieved a statistically significant TAT-ANC compared to placebo with a p-value of p<0.0001. The key secondary endpoint was also met with statistical significance, which lends to the ability of this drug to be able to do well in treating this WHIM syndrome patient population. It was noted that mavorixafor achieved statistical significance of TAT-ALC (Absolute lymphocyte Counts) threshold of 1,000 cells per microliter (lymphopenia) over a 24-hour period at four time points throughout the 52-week trial as well. This is shown as follows:
- Mean [Average] TAT-ALC of 15.80 hours for those on mavorixafor
- Mean TAT-ALC of 2.75 hours for those on placebo
This secondary endpoint was also met with statistical significance with p-value of p<0.0001. As I have shown with respect to this data directly above, mavorixafor is a very strong drug in being able to treat these patients with WHIM syndrome. In addition, this also sets up a first for this indication. Mavorixafor is the first and only oral investigational drug to show durable improvements in both severe chronic neutropenia (low neutrophil counts) and lymphopenia (low lymphocyte counts).
Lastly, things got better when the company released additional infection metrics from this late-stage phase 3 study later on. Treatment with mavorixafor showed statistically significant and clinically meaningful improvements across a number of key infection metrics versus placebo. This was with respect to multiple measures such as: Rate of infections, severity of infections, Duration of infections and other infection metrics. I believe there is a good chance that mavorixafor should be approved by the FDA for WHIM syndrome. Not just because of the efficacy data that was achieved, but also because of the excellent safety profile. Consider that there were no drug-related serious adverse events noted in this study at all. Not only that, but there were no dose limiting toxicities and no discontinuations either. Finally, it was stated that approximately 90% of patients in this 4WHIM phase 3 trial moved on to the open-label treatment portion of this study.
Additional Late-Stage Study Potential Further Adds To Value of This Biotech
The ability to advance mavorixafor for the treatment of patients with WHIM syndrome isn't the only positive advancement that this company has going for itself. It is also exploring the use of mavorixafor for the treatment of patients with idiopathic, cyclic, or congenital chronic neutropenia as a monotherapy or administered concurrently with injectable granulocyte colony-stimulating factor ("G-CSF"). Why is there a need to also bring up this program for the near-term? That's because there are two catalyst opportunities for investors to look forward to in the coming months. The first catalyst opportunity would be with respect to clinical data to be released. That is, X4 Pharmaceuticals is expecting to release results from an ongoing phase 2 study using mavorixafor for this chronic neutropenia patient population, in Q2 or Q3 of 2023.
At either expected time point of such data release, it is also expecting to provide guidance on whether or not it will be able to initiate a phase 3 study using mavorixafor for these chronic neutropenic disorder patients as well. It's hard to say how this drug will ultimately do with respect to this specific chronic neutropenic patient population, but it is my belief that is should do very well. The reason why is because as I displayed above in the clinical data, it has already shown that its drug is good at keeping neutrophil counts at needed levels in WHIM syndrome. In addition, Positive results were already released from a phase 1b study using mavorixafor to treat idiopathic, cyclic, or congenital neutropenic patients. It was shown that these patients did well when they either took mavorixafor monotherapy or if they took it concurrently with G-CSF. Why is there huge value potential with mavorixafor with respect to WHIM syndrome and other chronic neutropenic disorders? That's because this drug could end up being the first oral treatment for chronic neutropenic disorders. Current treatment options for CN disorders are injectables and even then, they are not that safe/tolerable for patients to take. In essence, should X4 Pharmaceuticals succeed, then it could change the treatment landscape for CN.
Financials
According to the 10-Q SEC Filing , X4 Pharmaceuticals had cash, cash equivalents and restricted cash of $94.4 million as of March 31, 2023. It should have cash for the time being, however, I believe that it will need to raise cash at some point in the 2nd half of 2023. The reason why I state that is because it states in its 10-Q SEC Filing that it has enough cash to fund its operations until at least Q2 of 2024. It will soon need to raise cash through equity offerings, debt financing, other third-party funding, marketing and distribution arrangements and other collaborations and strategic alliances. It is crucial that it does one of these financing events before the end of 2023. Why is this the case? That's because in its Second Amended and Restated Loan and Security Agreement with Hercules Capital Inc., it is required to maintain a minimum level of cash of $20 million on hand, which could be reduced to $10 million upon achieving operational milestones. If it is not able to raise cash by Q1 of 2024 to meet the covenant of this loan agreement, then the lender could require repayment of all outstanding debt.
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 NDA submission of mavorixafor for the treatment of patients with WHIM syndrome. Even if the NDA of this drug for this patient population is submitted by the 2nd half of 2023, there is no guarantee that the FDA will accept it in its present form. In addition, there can be no assurance that this biotech will ultimately receive FDA approval of mavorixafor for these patients with WHIM syndrome. A second risk to consider would be with respect to the ongoing phase 2 study of mavorixafor for the treatment of patients with idiopathic, cyclic, or congenital chronic neutropenia.
There is no way of knowing if the data to be released from this mid-stage study is going to be positive. Even if results are positive, there can be no assurance that the FDA will allow X4 Pharmaceuticals to advance the use of this drug for this patient population into a phase 3 study. The final risk to consider would be with respect to the financial position that this biotech is in. That's because as I stated above, it has a stipulation with its loan agreement that it must maintain at least $20 million on hand, which could be reduced to $10 million should it meet certain operational milestones. Regardless, if it can't raise cash on time by Q1 of 2024, then it may be required to pay all outstanding debt to Hercules Capital.
Conclusion
The final conclusion is that X4 Pharmaceuticals is a good speculative biotech play to look into. The reason why I state that is because its drug mavorixafor has the opportunity to change the treatment landscape of chronic neutropenia ("CN"). This all has to do with the ability to not only provide an oral drug option for these patients, but a treatment which might provide superior safety over existing therapies. It is well on its way towards this goal, especially when talking about mavorixafor being used for the treatment of patients with WHIM syndrome. It not only achieved the primary endpoint of the 4WHIM phase 3 study as noted above, but it also showed the drug to be safe/tolerable for patients to take as well. Being that proof-of-concept was established in using mavorixafor for the treatment of patients with WHIM syndrome, then I don't see why it can't also be used to treat patients with other chronic neutropenic disorders. With an NDA of mavorixafor for the treatment of WHIM syndrome expected in the 2nd half of 2023, plus the potential of advancing another phase 3 study of mavorixafor in patients with certain chronic neutropenic disorders, these are the reasons why I believe that X4 Pharmaceuticals is a good speculative biotech play to look into.
For further details see:
X4 Pharmaceuticals: Mavorixafor Could Change Chronic Neutropenic Treatment Landscape