2023-05-18 11:27:48 ET
Summary
- Celldex Therapeutics is at the forefront of the immuno-oncology revolution, leveraging its innovative pipeline to develop groundbreaking immunotherapies for the treatment of cancer.
- The company's flagship product, CDX-585, combining PD-1 and ILT4 blockade, has the potential to overcome immunosuppressive signals and enhance immune response.
- The company's recent press release highlighted positive data from the Phase 1b study of barzolvolimab, showcasing its potential to bring meaningful improvements to patients suffering from chronic spontaneous urticaria.
Celldex Therapeutics ( CLDX ) possesses a portfolio of groundbreaking products that harness the power of the immune system to combat cancer. Two standout candidates, varlilumab and CDX-1140, are at the forefront of Celldex's innovative approach. Varlilumab, an agonist antibody targeting CD27, has demonstrated exceptional immune activation properties and enhanced anti-tumor responses. Its ability to stimulate T cell activation, cytokine production, and tumor infiltration sets it apart from competitors' CD27 agonist antibodies. The recent clinical results of varlilumab showcase its potential as a superior candidate in immuno-oncology, paving the way for Celldex to lead the charge in this transformative field.
Cash Reserves Ensure Stable Future
At the end of March 31, 2023, Celldex had a cash position totaling $278.4 million in cash, cash equivalents and marketable securities; this was lower than that at the end of 2022 when it reached $305.0 million. Partially offsetting this decrease were proceeds from stock issuances under employee benefit plans, as well as unrealized gains associated with higher interest rates. Additionally, there were 47.2 million shares outstanding - a reflection of the company's capital structure. During the quarter, revenue grew significantly compared to the same period the year prior; instead of registering at just $0.2 million, it ended up reaching $1.0 million due to services performed under its manufacturing and research and development agreement with Rockefeller University.
In the first quarter of 2023, Celldex invested $26.8 million on research and development (R&D), an increase from the prior year's R&D figure of $17.1 million. This can be attributed to barzolvolimab-related clinical trial costs, contract manufacturing costs, and personnel expenditure. It is important for them to maintain effective resource allocation and assess potential financial returns for any investments made.
General and administrative (G&A) costs incurred in the first quarter of 2023 were $6.6 million, slightly lower than the $6.9 million that was allocated in the corresponding time-frame of 2022. This drop can be largely attributed to reduced legal fees, despite an uptick in stock-based compensation costs. Thus, it is key for the company to adequately manage G&A costs to optimize resource usage and keep operational expenses at a minimum.
Regarding fair value remeasurement of contingent consideration, Celldex noted a gain of $0.5 million in the three months ending March 31, 2022. This gain was primarily caused by changes to discount rates and highlights the impact of economic forces on the organization's financials.
Ultimately, the net loss for the first quarter of 2023 was reported to be $29.4 million, or ($0.62) per share, which is greater than the net loss of $23.1 million, or ($0.49) per share, recorded during the same period in 2022. Yet, many biopharmaceutical companies experience losses in early stages due to high R&D expenses and risks linked to drug creation. Therefore, for long-term success, Celldex should focus on achieving developmental targets and enhancing its product portfolio to drive future revenue growth and break even.
Additionally, Celldex provided financial guidance stating that their cash reserves as of March 31, 2023 will be sufficient to fund planned operations through 2025 and cover all working capital requirements.
Unique Antibody Products
Celldex is developing two significant products in its pipeline : barzolvolimab and CDX-585.
Barzolvolimab, a humanized monoclonal antibody , targets the KIT receptor found in various cells, including mast cells associated with inflammation. This drug aims to regulate mast cell differentiation, tissue recruitment, survival, and activity by inhibiting the KIT receptor . It is being investigated as a treatment for chronic spontaneous urticaria ('CSU'), a condition marked by persistent hives or wheals without discernible causes. Barzolvolimab has demonstrated encouraging outcomes in clinical trials , exhibiting quick and long-lasting effects. In both Phase 1b and Phase 2 trials , it showed significant symptom reduction and disease control, including complete responses and well-managed disease. It has also displayed a positive safety profile with good tolerability. Celldex intends to conclude enrollment for the CSU study by Q3 2023, with the expectation of announcing topline results in late 2023 or early 2024.
CDX-585, a bispecific antibody , merges PD-1 blockade with anti-ILT4 blockade , targeting immunosuppressive signals in both T cells and myeloid cells. ILT4 is a rising immune checkpoint found on myeloid cells. CDX-585 has finished Good Manufacturing Practice ((GMP)) production and Investigational New Drug ((IND))-enabling research. It is initially being explored for treating solid tumors, either as a standalone therapy or in conjunction with other cancer treatments. Clinical trials for CDX-585 involving patients with advanced malignancies are anticipated to begin in mid-2023.
Additional studies for barzolvolimab are ongoing in chronic inducible urticaria and prurigo nodularis. Celldex has finalized enrollment in the Phase 1b trial for chronic inducible urticaria, with plans to share data at a medical conference. The Phase 1b trial for prurigo nodularis has concluded enrollment, and study results will be disclosed in the final quarter of this year. Moreover, Celldex aims to launch a Phase 2 trial for barzolvolimab in eosinophilic esophagitis in June 2023.
Positive Results from Phase 1b Trial of Barzolvolimab
Celldex Therapeutics has unveiled updated findings from their Phase 1b clinical study of barzolvolimab for individuals with moderate to severe chronic spontaneous urticaria who are resistant to antihistamines. Barzolvolimab's distinct mast cell depletion mechanism presents a valuable alternative for patients unresponsive to existing standard treatments, including omalizumab .
The findings reveal notable symptom improvement across all examined dose levels, with ongoing activity seen in the 1.5 mg/kg and higher dose groups. The decrease in the urticaria activity score over a 7-day period (UAS7) at week 12 was considerable, varying between 67% and 82% among the dose groups. Complete response rates (UAS7=0) at week 12 were also noteworthy, ranging from 44% to 67%. Well-managed disease (UCT? 12) was attained in 63% to 89% of participants at week 12. Crucially, these responses were long-lasting, as patients maintained complete responses for up to 24 weeks, even after the final dose. Barzolvolimab's safety profile remained positive, with the majority of adverse events being mild or moderate in intensity and resolving during the study.
These compelling clinical findings bolster the ongoing Phase 2 trials of barzolvolimab in chronic urticaria and the extension of its development into additional mast cell—related indications . The results underscore the potential of barzolvolimab to offer extended symptom relief and enhance the quality of life for patients affected by mast cell-driven conditions. Celldex is optimistic about barzolvolimab's potential and anticipates completing the Phase 2 CSU study by the close of the third quarter, with topline data expected in late 2023 or the first quarter of 2024.
The remarkable clinical efficacy and sustained durability demonstrated by barzolvolimab, combined with its well-accepted safety profile, establish it as an encouraging treatment option for CSU patients. These advancements reaffirm Celldex's role as a crucial player in the realm of mast cell-related disorders and emphasize the company's dedication to promoting novel therapies in this domain. With ongoing research and additional data presentations planned, Celldex is well-prepared to make substantial contributions to enhancing patient outcomes and addressing unfulfilled needs in this sector.
Antibodies Can Be Risky
The concerns with the KIT inhibitor lie in its safety and efficacy. While the clinical data presented so far demonstrate a favorable safety profile, continuous monitoring is necessary to identify any potential adverse events or side effects that may arise with prolonged use or in larger patient populations. In terms of efficacy, although the drug has shown promising improvements in patients with chronic spontaneous urticaria, there is a possibility that it may not exhibit the same level of effectiveness in all patients or that its efficacy may diminish over time. The durability of the response and the long-term benefits need further investigation. Additionally, it is important to consider the drug's effectiveness in other mast cell-related diseases, as there may be variations in response and clinical outcomes across different disease indications.
A concern regarding CDX-585, on the other hand, is the potential for immunotoxicity. Targeting both T cells and myeloid cells can have systemic effects on the immune system, leading to immune-related toxicities or off-target effects. It is crucial to carefully monitor patients for any signs of immunotoxicity. Another concern is related to the use of CDX-585 in combination therapy for solid tumors. While the drug is expected to be developed as a monotherapy or in combination with other oncologic treatments , the success of combination therapies depends on factors such as drug interactions, optimal dosing regimens, and patient selection. The complexities of combination therapy may introduce challenges in terms of efficacy, safety, and overall clinical outcomes.
Celldex Trumps Competitors
In the case of varlilumab, which is an agonist antibody targeting CD27 , there are other companies developing similar immune checkpoint agonist antibodies. For example, Pfizer ( PFE ) has a CD27 agonist antibody called PF-04518600 in development. While both antibodies target CD27, Celldex's varlilumab may have certain advantages. Varlilumab has demonstrated potent immune activation properties and enhanced anti-tumor responses in preclinical and clinical studies. It has shown the ability to stimulate T cell activation, cytokine production, and tumor infiltration, leading to improved anti-tumor efficacy. These unique properties of varlilumab could contribute to its potential superiority over competitors' CD27 agonist antibodies.
Regarding CDX-1140 , which is a CD40 agonist antibody, there are several other companies developing CD40 agonist antibodies as well. For instance, Roche ( RHHBY ) and Pfizer have CD40 agonist antibodies in their pipelines. However, CDX-1140 may have distinct advantages. CD40 agonist antibodies have the potential to activate antigen-presenting cells and promote immune responses against tumors. CDX-1140, specifically designed to enhance CD40 signaling, has shown potent immune activation and anti-tumor activity in preclinical studies. It has demonstrated the ability to induce dendritic cell maturation, increase T cell priming, and enhance anti-tumor immune responses. These unique properties of CDX-1140 may position it as a superior candidate compared to competitors' CD40 agonist antibodies.
Conclusion
With a robust pipeline of innovative immunotherapies, Celldex is strategically positioned to capitalize on the growing demand for effective cancer treatments. The recent clinical results of their lead candidates, varlilumab and CDX-1140, demonstrate their potential to revolutionize immuno-oncology and pave the way for groundbreaking advancements in cancer care.
Celldex's financial management and prudent allocation of resources provide a solid foundation for future growth. The company's ability to secure funding, attract partnerships, and navigate the competitive landscape of biopharmaceuticals underscores its commitment to advancing its pipeline and achieving key milestones. With a keen focus on scientific excellence and meticulous clinical development, Celldex has established itself as a frontrunner in the field of immuno-oncology.
For further details see:
Celldex Therapeutics: Revolutionizing Cancer Care With Innovative Immunotherapies