RXi leveraging European partnerships to focus on new cancer treatments
Courtesy | RXi Pharmaceuticals
RXi Pharmaceuticals President and CEO Geert Cauwenbergh.
Marlborough-based RXi Pharmaceuticals is forging ahead into new territory to create new cancer treatments using its RNAi technology. That technology has already been proven successful in the treatment of warts, and now the company is focusing on the lucrative cancer-curing market. President and CEO Geert Cauwenbergh spoke to the WBJ about the company’s recent success since announcing the shift in January.
It's been about four months since the company pivoted to focus on cancer treatment. How is that going so far?
To be clear, the company was developing three therapeutic programs prior to our announcement in January. These included dermatology, ophthalmology and immuno-oncology. As a very small company, it was not possible for us to effectively continue to develop all three of these franchises in parallel. As such, after a thorough assessment, our team determined the potential to add the greatest value to patients and our shareholders was to exclusively focus on our immuno-oncology program. Since we had already established the chemical modifications we are using to synthesize our therapeutic compounds were safe and well tolerated in clinical trials by direct local injection, we were well prepared to move without delay into the development of immune-based therapies to treat cancer. Our platform technology has garnered a tremendous amount of interest from leading international cancer centers and cancer-focused biotech and pharmaceutical companies. The results stemming from these existing collaborations should allow us to quickly advance our development initiatives and enter the clinic in 2019.
What is the status of the other businesses the company was operating, namely the dermatology and ophthalmology businesses?
Over the course of the last several months, and most recently at the International Investigative Dermatology conference in May, the company has reported positive results from its dermatology franchise, including a Phase 2 trial for hypertrophic scarring with RXI-109, a Phase 2 trial for cutaneous warts with Samcyprone and a consumer testing program with a cosmetic ingredient to aid in the reduction of pigmentation, RXI-231. We anticipate our ophthalmology study will be reporting toward the end of the second quarter, which should allow us to also advance discussions in that area. Based on the availability of these study results, we have started a partnering process for each of the franchises and are aiming to monetize them in the course of the next several months, which should provide non-dilutive cash to support on our activities in immuno-oncology.
How close is the company to going to the market with a new drug or cancer treatment?
RXi is well positioned to be successful in the area of immuno-oncology with the potential to deliver its first new treatment option for patients relatively quickly compared to the development timelines for other therapeutic areas. Indeed, the development landscape for cancer therapeutics has improved substantially over recent years as we have seen by active government support (Cancer Moonshot) and expedited reviews by the Food & Drug Administration and recent approvals in ACT (Novartis, Kite). Again, RXi has demonstrated its proprietary sd-rxRNA therapeutic platform is safe and effective by direct local injection in Phase 2 clinical trials. Therefore, we are leveraging our proven technology platform, through internal efforts and external collaborations, to evaluate and develop a number of new treatment options as quickly as possible.
To date, what studies have proven the company's cancer treatment methods effective?
RXi’s sd-rxRNA therapeutic platform can penetrate immune cells and selectively block the expression of proteins to enhance the activity of these cells. Our current development initiatives focus on improving adoptive cell transfer (ACT) methods. For example, we can weaponize therapeutic immune effector cells to attack cancer through immune checkpoint inhibition with our sd-rxRNA. Building upon our proven platform, we have demonstrated in a cancer setting:
- sd-rxRNA therapeutic compounds can transfect cells with nearly 100 percent efficiency with little to no cell loss;
- sd-rxRNA therapeutic compounds can target multiple immunosuppression pathways (both extra- and intra cellularly) in a single therapeutic entity. This is major competitive advantage over current treatment modalities (i.e. antibodies);
- In an ovarian cancer model, meso-CAR T cells treated with sd-rxRNA targeting PD1 demonstrated a reduction in tumor growth as compared to control; and
- In a melanoma model, sd-rxRNA targeting PD 1 in tumor infiltrating lymphocytes (TILs) demonstrated enhanced tumor killing of these autologous tumor cells.
The effects of using RNAi in reprogramming immune cells to improve their potency in attacking tumor cells has been published in several peer-review journal publications. To date, we have shown broad applicability of sd-rxRNA in human T cells, NK cells, engineered cells and dendritic cells -- meaning we have numerous development options both internally and through partnerships and collaborations to empower existing clinical treatment paradigms and expand the applicability of engineered cells.
Is RXi well-positioned to develop its products without taking in revenue?
As a publicly traded small biotech company, attracting long-term value investors and maintaining sufficient capital to support development initiatives can be a challenge. Many small companies face this hurdle and this, in some cases, may thwart efforts in bringing new therapies to patients. That being said, our near-term goal is to extend our financial runway through business development activities that could generate non-dilutive cash infusions. In the future, we may also access the capital markets to raise additional funding from healthcare-focused value investors who support our long-term development goal to provide patients battling terminal cancers with powerful new treatment options that attack cancer going beyond current treatment modalities.
Are there partnerships or collaborations RXi is eyeing to help facilitate a marketable product?
As previously mentioned, we have a number of ongoing collaborations with leading international cancer centers and cancer-focused biotech and biopharmaceutical companies to explore and advance cell-based therapies with the sd-rxRNA platform for checkpoint inhibition as well as for inhibition of targets involved in cell differentiation and exhaustion pathways with the aim of improving fitness and potency of the cell product. RXi’s sd-rxRNA compounds are currently being developed to target PD-1, TIGIT and other important targets in immune effector cells.
Partnerships with leading cancer centers and larger companies with focus on immunotherapy will help us to become a key player in a large market with significant unmet needs. To date, we have secured the following:
- PCI Biotech: A collaboration is underway with this biopharmaceutical company located in Norway, to evaluate technology compatibilities and synergies between our respective technology platforms for the potential applicability of combination therapy in immuno-oncology.
- Gustave Roussy: This leading Comprehensive Cancer Centre in Europe is evaluating the potential of RXi's novel sd-rxRNA technology platform for use in cancer treatments.
- Center for Cancer Immune Therapy (CCIT) at Herlev Hospital: Based in Denmark, CCIT is a leading European center evaluating the potential of the sd-rxRNA technology platform in TILs for the use in treatment for a number of cancer types including melanoma and ovarian cancer.
- Medigene AG: A German-based biotechnology company is exploring potential synergies of using sd-rxRNA in combination with Medigene's recombinant TCRs to develop modified T cells with enhanced efficacy and/or safety.
- Iovance Biotherapeutics: A California-based company evaluating the potential synergies with RXi's novel sd-rxRNA therapeutic compounds and Iovance's autologous cell therapy based on tumor-infiltrating lymphocytes (TILs) for the use in the treatment of cancer.
What makes RXi's science standout from other companies hoping to beat cancer?
RXi is actively working to optimize various ACT platforms utilizing our novel self-delivering RNAi (sd-rxRNA) technology. The sd-rxRNA therapeutic platform differs from natural and most synthetic RNAi molecules in they are chemically modified to allow for efficient internalization of the compounds by cells and silencing of the targeted genes. For ex vivo cell-based therapeutic applications, our compounds do not require delivery vehicles, which is a major advantage since delivery vehicles can have related toxicity that affects cell viability. We have shown our sd-rxRNA has nearly 100 percent transfection efficiency with high cell viability in numerous cell types, including T cells, TILs, NK cells and CAR T.
What RXi has to offer over current innovations in cancer treatment can be divided in two large groups: direct interference with the tumor biology (e.g. through checkpoint inhibition) and changing the way our own immune cells can attack tumors (e.g. through impacting cell differentiation and/or metabolism).
Not only can our sd-rxRNA compounds interfere with the tumor biology and hence be an alternative to those checkpoint inhibitors that may more readily allow for combinations of such inhibitors, but we can also weaponize our own immune cells better, resulting in a more efficient killing effect for those immune cells against the tumors. That means that our sd-rxRNA technology can also provide ways for treatments currently in development by other companies and academic institutions to become more powerful/effective.
Due to the unique characteristics of our sd-rxRNA technology, it is well-suited for the development of immune-based cancer therapies, and we are very excited to be advancing this program as part of the entire industry’s efforts to address the global epidemic that cancer has become.
This interview was conducted and edited for length and clarity by WBJ Staff Writer Zachary Comeau.
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