Advaxis: Taking Noteworthy Strides In Bone Metastasis

| About: Advaxis Inc. (ADXS)

Summary

Advaxis has developed anticancer vaccines for a diverse range of tumors.

Recently, ones of its candidates received orphan designation, and an early stage trial was initiated.

Bone metastasis represents a significant clinical challenge in breast cancer therapy.

Anticancer vaccines have been picking up steam lately, with the ongoing study of various platforms like live tumor cell vaccines (such as GVAX pancreas, which I covered briefly in a previous article). This technology relies on taking tumor cell lines (or, in some cases, live tumor samples from patients) and modifying them so they can be transplanted into a patient to promote an immune response. The hope with vaccines is to train the body to recognize and destroy the tumor. Advaxis (NASDAQ:ADXS) is one of the key players in developing these vaccines.

Beyond live-tumor vaccines, though, there are other interesting platforms being explored. One such technology is live, attenuated Listeria monocytogenes. In this case, researchers will remove one or more genes that allow Listeria to be infectious. Then, they will insert a plasmid or gene that forces the Listeria to inject a protein associated with the tumor into immune cells inside the body. Basically, they're subverting the machinery of natural Listeria and turning it into a robust trainer for the body.

I've gone over the so-called LADD platform of Aduro Biotech previously. One may look at these two companies and assume they have very similar technologies and therefore are in direct competition. Interestingly, this is not the case. The Listeria vector used by Advaxis differs in two key ways from LADD: first, only one virulence gene is deleted. Second, Advaxis adds a plasmid into these bugs that forces them to make a lot more of the protein that they're training the immune system to recognize and destroy. The hope is create an even more robust tumor response. Still, any comparison with respect to potential efficacy right now is pure speculation, so I won't go into that. Suffice it to say, the two Listeria platforms are notably different.

The types of cancer these companies are pursuing are also quite varied. Whereas Aduro is tackling tumor types like pancreatic and mesothelioma, Advaxis has taken a different track and targets more common tumor types like breast and cervical cancer. Our specific topic for discussion today is HER2-positive breast cancer.

Enter ADXS-cHER2

ADXS-cHER2 is a Listeria-based vaccine that makes a fragment of HER2 fused to a protein called listeriolysin, which acts as a sort of catalyst for the immune system to recognize and fight the fragment in question. If successful, these bacteria will train the immune system to identify and destroy HER2-expressing cells. The obvious contender here would thus be HER2-positive breast cancer, which accounts for anywhere between 15% and 20% of all cases. It is a highly aggressive form of breast cancer, but it is, at this time, treatable with available chemotherapy and anti-HER2 antibodies like Herceptin and Perjeta. They're not perfect, however. Only around half of the patients with HER2-positive breast cancer see benefit from Herceptin.

Importantly, the development of bone metastasis remains a substantial challenge for patients with HER2-positive disease. Bone disease can lead to osteoporosis, fractures, and substantial pain. Moreover, there are few treatments available to address these metastases. This makes this disease state an important unmet need in breast cancer therapy and an attractive target for small caps like Advaxis.

Trials and Early Findings in Bone Cancer

In an effort to demonstrate its potential in bone cancer and metastasis, Advaxis has initiated studies in osteosarcoma, which can overexpress HER2 in as many as 30% of cases. To this end, the company has initiated clinical studies of their HER2 vaccine in children with this disease. Data for this study are anticipated, but Advaxis made recent headlines with publication of a clinical trial in a dog model of osteosarcoma. These dogs were given the vaccine after definitive treatment for osteosarcoma, either with chemotherapy or amputation.

In 15 out of 18 dogs tested, the vaccine led to a specific anti-HER2 immune response within 6 months post-treatment. Compared with historical controls, the vaccine appeared to lead to reduced rates of disease metastasis and increased survival time. These findings definitely bode well for patients with osteosarcoma and HER2-positive metastatic breast cancer. While early, they strongly justify the further study of this vaccine in human trials. Also importantly, the risk of toxicity from the Listeria vaccine was minimal in canines, which is going to be an important parameter for human studies.

The Market for Bone Metastasis

So where does this early success place Advaxis's therapy for bone disease in the greater context? Currently, there are 2 approved therapies for bone cancer in the United States. One is levoleucovorin, which has been used for a long time in conjunction with chemotherapy as a supporting agent. The other big player is denosumab, an inhibitor of RANK ligand. But this agent is designed more for preventing bone degradation and osteoporosis secondary to cancer, rather than fighting the cancer itself. Chemotherapy in general is the only known effective treatment modality, with the resultant risk of toxicity. Considering that children are the target for this form of osteosarcoma, this becomes even more important, since long-term toxicity can be debilitating for children, resulting in developmental issues, among other challenges.

This means there is a gap to be filled by targeted and immunologic therapies in the space of osteosarcoma. This is an orphan indication, so it's relatively rare, but the FDA puts a high priority on finding life-saving treatments for rare diseases. Moreover, if proof of concept can be established in osteosarcoma, it may ease the regulatory pathway for this vaccine in the bone metastasized HER2-positive breast cancer space. A phase 1/2 study is already underway for the treatment of HER2-positive breast cancer, though no results have yet been posted.

Conclusions

So where should Advaxis land on your biotech investment radar? With a nearly $300 million market cap, $100 million cash on hand, and a burn rate of nearly 20 million per quarter, the leeway Advaxis has is a little tight. However, it has secured partnerships for developing its vaccines with numerous companies to help ease the developmental costs. In recent years, Advaxis has successfully completed a number of stock sales to put cash in its coffers. It may yet need to do that again as it endeavors to get those key efficacy data for its vaccine therapies. If it's successful, I have little doubt Advaxis will be able to secure a partnership from an interested pharmaceutical player.

So should you invest in Advaxis at this time? That depends on your tolerance for risk. True, oncology products can move quite quickly if they show promise in tumors that are unmet needs, but that relies on really good clinical data. Given what Aduro has seen in its LADD technologies, there seems to be promise. I would take what you've read here with a grain of salt as you build a full picture of due diligence for Advaxis.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.