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Anexon company (Nasdaq: Supplement) was able to achieve positive results from a phase III study for the treatment of patients with Guillain-Barré Syndrome (GBS). In fact, she noticed that the dose of her medication was 30% lower mg/kg ANX005, was able to meet the primary endpoint of this study with statistical significance.
If so, what upside can investors expect in the coming months? Well, there are three more milestones, which I think could enhance shareholder value even further. The first thing to note is that the full data set from this phase III study, which was conducted in the Philippines and Bangladesh, will be presented at the upcoming 2024 Peripheral Nerve Society Annual Meeting on June 25.
The reality is that a phase III study will not be the case It is enough to gain FDA approval for ANX005 to treat these GBS patients. The good news is that it has already received agreement with the US Food and Drug Administration (FDA) that a real-world evidence (RWE) protocol using the International Guillain-Barre Syndrome Outcome Study (IGOS) will be sufficient to submit a BLA application.
Having said that, data from the phase III IGOS trial are expected to be released in the first half of 2025. If the primary endpoint is met here as well, a BLA for ANX005 will be offered to GBS patients over the same time period. .
These are two other catalysts that investors should keep an eye on. The premise of this biotechnology is not only limited to developing ANX005 to treat patients with GBS. This is just one part of a pipeline using Cq1 complement inhibition, which appears to have demonstrated proof of concept in GBS.
Another promising program using this technology is the development of ANX007, which is expected to soon be advanced into two phase III studies for the treatment of patients with geographic atrophy (GA). Both late-stage trials are expected to begin in the second half of 2024, which could also enhance shareholder value.
ANX005 could be a major game-changer for Guillain-Barré syndrome patients in the United States
As I mentioned above, Annexon was able to report positive results from its Phase III study for the treatment of patients with Guillain-Barre Syndrome (GBS) with ANX005. Again, this was a study done on patients in the Philippines and Bangladesh. Although this is not an ideal position in terms of seeking immediate FDA approval, I can see an argument that it was the right thing to do in terms of compassion. GBS is more prevalent in these two geographic patient groups, for starters.
Secondly, these countries do not have access to adequate care. How is that? Well, keep in mind that both countries have limited access to standard of care (SOC) and intravenous immunoglobulin (IVIG). So, from a moral point of view, it was the right thing to do. Regardless, the FDA and Anexon have already reached agreement that the real-world evidence (RWE) protocol study, IGOS, will be sufficient to gain FDA approval upon successful completion. Guillain-Barre Syndrome (GBS) It is a type of disorder where the immune system attacks a person’s nerves. Although such an attack occurs either through a bacterial or viral infection.
The truth is that this disorder affects multiple aspects of a person’s body such as muscle movement control, pain signals, temperature and much more. As for movement problems, it can lead to paralysis in severe cases. I think the most important point of all is that there are no FDA-approved medications for GBS patients.
To see if ANX005 could truly treat these patients with Guillain-Barre Syndrome, it conducted a phase III, randomized, double-blind, placebo-controlled study. This trial randomized 241 patients 1:1:1 to receive one of the following doses:
- 30 mg/kg ANX005 – 80 patients
- 70 mg/kg ANX005 – 80 patients
- Placebo comparison – 80 patients.
The primary efficacy outcome measure was the GBS-DS scale score at week 8 of the drug versus placebo comparison. What is this metric, and why is it important? Well, the purpose of this scale is to measure patients’ ability to move freely. That is, to know the extent of the disability they suffer from in terms of muscle movement. Thus, the aim was to evaluate patients in terms of specific aspects of mobility, such as: good health status (normal and able to run), disability (aided walking and unaided walking), and severe disability/death (bedridden, ventilated, and death).
This statistically significant primary endpoint was achieved when patients were given the lower dose of 30 mg/kg of ANX005. That is, this dose of the drug showed that versus placebo, he was able to achieve a 2.4-fold improvement in the GBS-DS at week 8. This difference between drug versus placebo, with respect to the primary endpoint, It was statistically significant with p value = 0.0058. One potential confusion in clinical trials is why a higher dose would not be better than a lower dose. I can see the conflict here, but there is an explanation. The C1q inhibition achieved based on 30 mg/kg ANX005 over a 1-week period was better than 70 mg/kg ANX005 over a 2-3 week period.
The hypothesis here is that inhibiting C1q in the early phase of the disease, when the damage has just occurred, allows the drug to work faster during this phase (one week). As a longer period does not lead to sufficient inhibition of C1q. There are three rapidly approaching catalysts for this program. It is full data that will be presented at the medical conference, the final results of the RWW IGOS study program for ANX-005 for GBS, as well as the possibility of submitting a BLA. The first is expected to occur during this year, while the latter two are not expected to occur until the first half of 2025.
I feel as though this biotech is doing good things in terms of C1q inhibition of the cascade system as part of its technology. Also, this technology is also being used to target other disorders in its pipeline such as Geographic Atrophy (GA). The reason you’re excited here is because the company found a way to ban the entire sequel series, not just a portion of it. What do I mean by this exactly? Well, there are drugs that only target a specific aspect of the complement cascade, such as C5 or C3. With Annexon targeting Cq1, it removes all cascades at the source.
Consider the hypothesis that the cascade system starts at C1q and works its way down to C4, C2, C3, C5, and C9. By taking a signal of the disease from the source, it can help patients adequately. Speaking of targeting geographic atrophy, this company’s goal is to start two late-stage studies within this year, using ANX007 to treat these patients. One phase III study that will be launched is known as ARCHER II in mid-2024, which uses this drug versus a sham control.
The other late-stage trial, known as ARROW, will test this drug against it It will save (It is already approved to treat patients with GA), which will serve as a head-to-head comparative study. One final potential milestone to consider regarding ANX007 for GA is an R&D day to be held in mid-2024.
Finance
According to the 10-Q SEC FilingAnnexon had cash, cash equivalents, and short-term investments of $264.9 million as of March 31, 2024. This company has been able to finance itself over the years by either selling shares of its common stock or issuing shares under a mark-to-market (ATM) agreement. . It believes that its available cash is sufficient to finance its operations until mid-2026.
As you can see, it still has a lot going for it Cash runway In the foreseeable future. However, if management deems it necessary, it can decide to collect cash through the use of its ATM agreement. This will be in connection with the ATM offering agreement entered into with TD Cowen in March 2024, whereby it can occasionally sell shares of its common stock for a maximum aggregate offering price of $100 million. As of March 31, 2024, no sales have been made under this 2024 ATM Agreement. that it Burn cash It is $28 million per quarter.
Risks to the business
There are several risks that investors should be aware of before investing in Anexon. the The first danger Something to consider will be the just reported positive results from a phase 3 study in Bangladesh and the Philippines, using ANX005 to treat patients with GBS. This is because this was just a proof-of-concept study that C1q inhibition works in treating these patients. To submit a BLA for ANX005 to the US Food and Drug Administration (FDA), it will have to demonstrate that this Phase III study is comparable to the RWS IGOS protocol established for marketing approval in the US. There is no guarantee that the functional improvement of this other phase III study will be achieved with statistical significance. What has been achieved with the Bangladesh/Philippines population will also not be observed in the Western population.
the The second danger An issue to consider would be targeting patients with geographic atrophy (GA) with ANX007. Although C1q inhibition has worked well in treating patients with Guillain-Barré syndrome, there is no guarantee that a similar or superior efficacy result will be observed in this other indication. On the other hand, one thing that sets this drug apart is that it is slightly different from ANX005. How is that? Well, keep in mind that ANX007 is an antigen binding fragment (FAB) antibody, while ANX005 is a monoclonal antibody. Therefore, this difference could be a factor in terms of the type of effectiveness that is produced in the outcome.
the The third and final danger Something to consider would be regarding competition in the supplement inhibitor space. As I mentioned above, it would be a potential contender in terms of targeting GA Abelis Pharmaceuticals (APLS) with Syfovre. This drug, which is approved to treat these patients, is a C3 inhibitor of the complement cascade system.
There have been many other complement inhibitors approved over the years to treat patients with various disorders. For example, Soliris was the first complement inhibitor drug approved and completed in 2007 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). From there, this has led to the ability to use complement inhibition against other rare disorders without approved drugs such as atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis (gMG) and more.
The point is that Annexon could counter such a risk if it could prove that inhibiting C1q, which occurs upstream of the complement cascade system, prevents inflammation downstream. If proven in other disorders, it could have a competitive advantage over all other complement inhibitors approved or in clinical development.
Conclusion
Annexon has been able to develop a good kind of technology when it comes to targeting the complement cascade system. Instead of targeting other factors that cause inflammation, it was able to go straight to the source by targeting C1q. Whether this mechanism of action (MOA) can be proven to work in terms of targeting other disorders remains to be seen, but the potential is there.
One of the main reasons I wanted to mention Annexon, Inc., even though it has already achieved positive results from a phase 3 Bangladesh-Philippines study using ANX005 to treat patients with GBS, is because of the many milestones expected in the near term. One of those milestones is expected to occur in 2024, and that will be the release of full data from the just-reported phase 3 study. From there, you have other RWS IGOS trial data and BLA registration expected in 2025. With proof of concept for C1q inhibition in a few indications like GBS and GA, as well as several milestones still to come, I think investors can capitalize on any potential gains achieved.
