For the past few years modifying T-Cells to express Chimeric Antigen Receptors, a practice known as CAR-T, has been the hottest space in cancer therapy. Through CAR-T therapy, there have been amazing strides made in saving patients suffering from cancers that, in the past, were incurable.
Companies focused on CAR-T have seen two products approved by the FDA with a pipeline of additional treatments expecting approval in the near future. The result of which has been huge stock market success for these companies. These include massive winners such as Kite and Juno, companies recently acquired for many billions of dollars, before achieving a single dollar of product revenue.
Development of CAR-T drugs typically takes many years and hundreds of millions of dollars, however ITUS Corp. (ITUS:NASDAQ) in collaboration with Moffitt Cancer Center has been able to develop its products for fractions of what others have spent. The CAR-T development path has seen both success and failure in clinical efforts. The major success stories have centered around CAR-T for liquid tumors. Sadly, there has been very limited success, despite the promise it holds, in developing CAR-T therapies for epithelial tumors.
On the other hand, ITUS Corp. is one company that has shown early promise with its solid tumor therapy program as it is developing a CAR-T treatment for ovarian cancer. In pre-clinical trials performed at Moffitt Cancer Center, ITUS has demonstrated amazing success, enough so that the company accelerated its development timeline by 12 months and is seeking a meeting with the FDA for discussion of its IND (investigational new drug application) later in 2018. This is incredibly positive, however the stock market seems to be ignoring ITUS' work as its valuation remains at levels far below those of peers with less impressive results.
In Tailwinds' opinion, ITUS suffers from a lack of investor belief in the program, probably due to the size of the company and the relatively small budget behind development. ITUS is taking a unique approach to developing its therapy and, frankly, the market doesn't seem to get it…Yet!
Therefore, in an effort to better understand the approach ITUS is taking to CAR-T, Moffitt's role in helping it bring this therapy to market, and why we believe it will ultimately be very successful, we spoke with Dr. Jose Conejo-Garcia, the principal investigator at Moffitt, who is focused on ITUS' CAR-T therapy. What follows below are the highlights and key takeaways from our conversation.
Moffitt is looking to become the #1 CAR-T facility in the country
Before you can even consider that a company of ITUS' size can be successful in a massive undertaking like CAR-T, it is essential to know about its partner. Moffitt Cancer Center is one of the premier cancer research centers in the US. It is a state of the art facility and the only one in Florida that has achieved a National Cancer Institute designation.
According to Dr. Conejo-Garcia, the main thrust of Moffitt is on cancer trials, where it has become the market leader. Moffitt has worked with CAR-T innovators, including Kite, Novartis and Juno, in their pivotal trials. In addition, it has over 10 current clinical trials ongoing, along with a similar number of clinical trials using T cells engineered in different ways. In general, Moffitt has its fingerprints all over most of the important CAR-T work that is taking place.
Within Moffitt, Dr. Conejo-Garcia is co-leader of the Immunology Program and chair of the Department of Immunology since joining in 2016. He is also the principal investigator on the ITUS program.
Dr. Conejo-Garcia is a renowned expert in immuno-oncology, especially as it relates to ovarian cancer. Between his expertise and the extensive facilities at Moffitt, ITUS has managed to attract world-class partners to its project. For a small company like ITUS this is an amazing benefit, to be able to work with top experts. This is an opportunity not generally available for early stage cancer companies and speaks to the quality of the therapy being targeted as well as the respect Dr. Amit Kumar, ITUS' CEO, has from the medical community.
Targeting…the different approach ITUS is taking
Chimeric Antigen Receptor treatments have shown amazing efficacy in B-Cell cancers. This is due to the Antigen CD19, the target that all approved CAR-T treatments are shooting for. CD19 is found only on B-Cells. Thus, the killer T-Cells created in CAR-T treatments are like heat seeking missiles when it comes to B-Cell cancers; they go primarily after B-Cells and nothing else.
In solid tumors there is no "CD19" or equivalent thereof. True, researchers have found targets on solid tumors, however these same targets exist on other, healthy organs. The issue with solid tumor CAR-T therapies tried to date has not been killing cancer; it has been their efficacy in killing healthy organs. Instead of heat seeking missiles, they are more like napalm, attacking the whole body.
This is what makes ITUS unique from the competition. According to Dr. Conejo-Garcia, instead of targeting an antigen, ITUS has located a totally different target: the FSHR or Follicle Stimulating Hormone Receptor.
Dr. Conejo-Garcia says that over 60% of ovaries express the receptor for FSH. More importantly, it is not found elsewhere in women. Therefore, a T-Cell engineered to recognize and bind to the FSH receptor will become heat seeking missiles for the ovaries and not attack the rest of the organs in a body. This result was demonstrated in mouse models recently, where exactly 60% of the mice tested had efficacy in the ovaries with negligible side effects.
What about in humans? Can we trust mice?
According to Dr. Conejo-Garcia, mouse trials are a mixed bag when it comes to translating into success in humans. The good news is the models are quite predictive of efficacy. The bad news is they aren't very predictive of toxicity.
Which means that, in ITUS case, the great efficacy shown in mouse trials should translate into a product that attacks ovarian cancer in humans. But, although the lack of side effects means it didn't attack healthy organs in mice, can we expect that in humans?
Typically, the response would be "no" as mouse trials are inconclusive. However, Dr. Garcia believes that his trials to date were done in a manner that should enhance the translation of toxicity (or lack thereof) into humans. More exactly he said this…
"When we had selected sequences of FSH receptors in humans, we also generated reagents with the same sequence of domains in mice for those preclinical trials. By using mouse FSH, we can redact the trials back to humans with equivalent results, as these pathways are evolutively conserved."
In laymen's terms, this means Dr. Conejo-Garcia is highly confident that ITUS' CAR-T therapy's efficacy with lack of toxicity should translate very well from mouse to human trials.
What will the FDA think of the IND application?
One never knows where the FDA will come down on an application. However, in the case of CAR-T, the FDA has seen the efficacy and become very receptive towards new treatments of this variety.
In our conversation, Dr. Conejo-Garcia expressed confidence that the FDA would be receptive to ITUS' application. He gave me three reasons to think this might be the case:
- The efficacy shown has been outstanding and testing toxicity is very tough. The way they have worked with the mouse variant should be well regarded by reviewers.
- ITUS is proposing a dose escalating trial. This means that patients will start with low doses that get increased over time, allowing doctors to monitor the side effects and pull the plug if needed. This limits risks to patients.
- Finally, they are aiming to treat a disease in which patients have failed all other treatments. This is a disease that often results in death, so the risk/reward behind a trial is skewed in the patients' favor.
A solid (tumor) platform
In closing, Dr. Garcia talked about how targeting the FSHR could create a true solid-tumor CAR-T platform. His work has shown that FSHR exists on different tumors, yet not elsewhere in the body. As the first biotech targeting hormone receptors, not antigens, ITUS could be creating a whole new class of solid tumor CAR-T therapies.
Summary and Thank You!
The time spent with Dr. Conejo-Garcia last week was both educational and uplifting. I left the conversation with a much better understanding of the issues around CAR-T and why there have been limited successes in solid tumors.
I also had a greater sense in ITUS' strategy and greatly increased confidence that it is working with the right people and on the right path to success. CAR-T is an incredibly exciting area of cancer therapy and it's still in the early stages of understanding. The work done by Dr. Conejo-Garcia and the staff at Moffitt is amazing and will lead to many saved lives.
A very important point I want to underscore is the credibility of Moffitt. Even though ITUS is still a small company working in the hottest area of cancer research, it's important to note that the reputation and credibility of Moffitt Cancer Center is fully backing ITUS's efforts. Moffitt, and a world class team lead by Dr. Conejo-Garcia (which includes Dr. Linda Kelley, Dr. Marco Davila, Dr. Daniel Abate-Daga, and Dr. Robert Wenham) would not be approaching the FDA unless they had something special.
Meanwhile, as hot as CAR-T is for investors, and as strong as Moffitt is as a partner, ITUS manages to fly below the radar screen. I am very confident that we'll see an approved IND in the near future. With great results and a potential platform opportunity in solid tumors, investors will start to pay attention soon enough.
I'd like to thank Dr. Conejo-Garcia for his generously sharing his time with me. I look forward to watching his and ITUS' progress.
Daniel Carlson is the founder and managing member of Tailwinds Research Group and its parent company DFC Advisory Services, which is a licensed registered investment advisor (CRD # 297209). Tailwinds is a microcap focused research company that provides research on and consults to over 20 emerging growth companies in the technology and life sciences arenas. DFC Advisory Services is an RIA that manages money dedicated to investing in the companies covered by Tailwinds. For more information on these two companies and their track record, please see www.tailwindsresearch.com. Prior to founding these two entities, Dan spent many years working with small public companies, having been CFO of two public companies and helping finance many others. A 1989 graduate from Tufts University with a degree in Economics, Dan’s formative years in business were spent as an equity trader, first on the Pacific Coast Stock Exchange then on the buyside at several multi-billion dollar firms.
This article was submitted by Tailwinds Research. For more information on Tailwinds Research or on ITUS, please visit www.tailwindsresearch.com.
Tailwinds is engaged by ITUS Corp. and owns stock in the company. For a complete list of disclosures, please click here.[NLINSERT]
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