2023-11-08 15:22:43 ET
Summary
- Positive results achieved from phase 1b study using barzolvolimab for the treatment of patients with prurigo nodularis; Phase 2 multi-dose study to be initiated in early 2024.
- Positive results from a phase 2 study using barzolvolimab for the treatment of patients with chronic spontaneous urticaria achieved; CSU program ready for phase 3 study advancement.
- Goal to advance use of barzolvolimab for other mast cell disorder indications like eosinophilic esophagitis.
- CDX-585 is a bi-specific antibody targeting both PD-1 and ILT4 blockade being advanced for the treatment of patients with advanced or metastatic solid tumors who progress on prior SOC therapy; Phase 1 enrollment of dose-escalation ongoing.
Celldex Therapeutics, Inc. ( CLDX ) has been making great progress in advancing its pipeline by using barzolvolimab for the treatment of patients with a variety of types of mast cell disorders. In a Seeking Alpha article I wrote last year titled " Celldex: Barzolvolimab Plus Bispecific Antibodies Advancement, " I noted that the company had obtained positive data from a phase 1b study using this drug to treat both chronic spontaneous urticaria and chronic inducible urticaria. The progress with respect to this biotech advancing this drug has been highly ideal. That's because it just recently presented positive results from a phase 2 study, which used barzolvolimab for the treatment of patients with chronic spontaneous urticaria. Full 12-week data from this recently reported phase 2 study is going to be presented at an upcoming medical meeting.
Not only that, but it is now ready to advance the use of barzolvolimab to phase 3 clinical testing for this CSU program. However, I believe that this particular biotech has potential with other mast cell disorders besides these two mast cell disorder indications. This is evidenced by the release of results from the phase 1b study, which used barzolvolimab towards another mast cell disorder known as Prurigo Nodularis [PN]. Not only did the results show that this drug was able to reduce itching and improve skin clearance, but it is now being prepared to be advanced in a phase 2 subcutaneous multi-dose study, which is expected to start in early 2024. I believe that Celldex establishing itself in another mast cell disorder proves just how useful this drug is in being able to target and treat these particular disorders.
Barzolvolimab For The Treatment Of Patients With Prurigo Nodularis
As I noted above, Celldex has not only been able to achieve positive results with barzolvolimab just for the treatment of patients with chronic spontaneous urticaria [CSU] and chronic inducible urticaria [CIU], but also with respect to another mast cell disorder known as Prurigo Nodularis [PN]. That's because it just achieved positive results from a phase 1b study, using barzolvolimab for the treatment of this specific patient population. Prurigo Nodularis is a chronic skin disease characterized by the presence of itchy bumps known as nodules. This not just an itching that tends to go away. It is an intense type of itching that causes people to continue to scratch until pain or bleeding occurs. This biotech just recently achieved positive results from the phase 1b study, which used barzolvolimab for the treatment of these patients with PN. About 24 adults with PN were randomized in this phase 1b study across three different arms as follows:
- 9 patients given 3.0 mg/kg of barzolvolimab.
- 9 patients given 1.5 mg/kg of barzolvolimab.
- 8 patients given placebo.
Patients being given this drug achieved improvements of Worst Itch-Numerical Rating Scale [WI-NRS] and the Investigator Global Assessment [IGA] scale. Why is that? Well, it's all in the numbers that were presented with patients being evaluated with doses of 3.0 mg/kg - 1.5 mg/kg of barzolvolimab or placebo over an 8-week period. For instance, with respect to patients given either 3.0 or 1.5 mg/kg of barzolvolimab, 57% and 43% respectively achieved a ?4-point decrease in WI-NRS . On the other hand, only 25% of the placebo patients achieved such a measure. The same can be said for the other Investigator Global Assessment [IGA] endpoint measured.
With respect to IGA 29% of patients achieved a "clear" or "almost clear" skin at week 8. However, this was only observed in patients who were given a single dose of 3.0 mg/kg of barzolvolimab only. No patient that was given 1.5 mg/kg of barzolvolimab or placebo achieved IGA over an 8-week period. In my opinion, this data is very impressive. Why is that? That's because the data I just noted was only with respect to patients being given one dose of this drug only. The next phase 2 study using barzolvolimab for PN, which is expected to start in early 2024, is going to be a multi-dose one. Thus, it remains to be seen what happens when patients are given additional doses in terms of safety and efficacy.
Financials
According to the 10-Q SEC Filing , Celldex Therapeutics had cash, cash equivalents and marketable securities of $235.3 million as of September 30, 2023. It believed that it would have enough to fund its operations through 2025. However, this was not the case, because it just announced the pricing of a public underwritten offering . It is selling 7,425,000 shares of its common stock at a public offering price of $27 per share. In addition, it granted the underwriters a 30-day option to purchase up to an additional 1,113,750 shares of common stock at the very same public offering price.
The company believes that it could generate gross proceeds of approximately $200.5 million from this underwritten public offering. However, this doesn't include the exercise of the underwriters' option to purchase additional shares, nor does it contain the expenses to come about from this.
Risks To business
There are several risks that investors should be aware of before investing in Celldex Therapeutics. The first risk to consider would be with respect to the advancement of barzolvolimab for the treatment of patients with prurigo nodularis [PN], which was just tested in a phase 1b study. It is the idea of this company to begin a phase 2 subcutaneous multi-dose study for this program in the early part of 2024. Even though a single dose of barzolvolimab for the treatment of these patients was shown to be good, there is no guarantee that giving patients additional doses will result in an improvement for them.
The second risk to consider would be the use of this drug for the treatment of patients with CSU. That's because Celldex is gearing up to initiate a phase 3 study for this program. Even though this drug was shown to be statistically significant in phase 2 testing in terms of change from baseline to week 12 of UAS7 compared to placebo in these CSU patients, there is no assurance that a similar outcome will be achieved in phase 3 clinical testing.
The third and final risk to consider would be with respect to the use of barzolvolimab for the treatment of other mast cell disorders. Even though this drug has been shown to achieve positive data in several mast cell diseases thus far, there is no guarantee that other sub-indications will have a similar outcome. For instance, the company also wants to advance the use of barzolvolimab for the treatment of patients with eosinophilic esophagitis [EOE] in phase 2 testing. There is no guarantee that this drug will also end up performing well for this specific mast cell disorder patient population.
Conclusion
Celldex Therapeutics has made great progress in advancing its pipeline with the use of its drug barzolvolimab for the treatment of patients with mast cell disorders. Especially, when you consider the fact that it has already been able to report positive results in using this drug to treat several of them thus far. It has already been able to post positive data in being able to use this drug towards treating chronic spontaneous urticaria [CSU], chronic inducible urticaria [CIU], and prurigo nodularis [PN].
Matter of fact, it is ready to go with respect to being able to advance the use of barzolvolimab for the treatment of patients with CSU in a phase 3 study. The goal for it is to be able to target as many mast cell disorders as it can in just using this drug only. What is ideal about Celldex is that it is not only just going to rely on the use of this drug as part of its pipeline.
It is also exploring the use of a bispecific antibody, known as CDX-585, which is being used to treat patients with advanced or metastatic solid tumor patients who have already progressed on standard of care [SOC] therapy. The current status for this particular program is that the company is in the process of enrolling patients in the dose escalation portion of this phase 1 study.
Why I believe that this drug has potential is because it is a bi-specific antibody which is targeting both PD-1 blockade and anti-ILT4 blockade as well. Both of these targets have immunosuppressive effects against T-cell and myeloid cell responses against solid tumors. By going after both of these blockades at the same time, it is quite possible that CDX-585 might be able to help these advanced or metastatic solid tumor patients.
For further details see:
Celldex: Mast Cell Disease Targeting Continues To Make Advancements In Clinic