Uppsala-based DexTech Medical conducts research and development in oncology based on a proprietary CDC (carbohydrate-drug-conjugate) platform called GuaDexThe backbone of GuaDex consists of clinical Dextran which has been shown to be well suited for conjugation, i.e. conjugation with other molecules. Dextran is a well-known drug that was launched in the 1950s, among other things as a blood substitute.
GuaDex generally has tumor-specific and tumor-toxic properties and selectively binds to malignant tumor cells. By coupling active substances to Dextran, the drug's properties and treatment effect can be enhanced or changed, while side effects can be minimized.
OsteoDex – the company's lead candidate
Based on the CDC platform, DexTech has developed four different drug candidates. The lead candidate has come the furthest. OsteoDex, which was primarily developed for the treatment of bone metastases in castration-resistant prostate cancer (mCRPC). In OsteoDex, GuaDex is linked to the bisphosphonate alendronate, which allows the candidate to bind to the parts of the skeleton that have been attacked by daughter tumors. The drug candidate also contains Guanidine, which contributes to the cytotoxic effect.
OsteoDex has been evaluated in a Phase IIb clinical study with good results showing that the bifunctional mechanism of action has a clear tumor-inhibiting effect and a very good safety and tolerability profile, with only few and mild side effects.
Multiple myeloma is the next area of focus
To further demonstrate OsteoDex's potential as a cancer drug, DexTech has chosen to expand the clinical program to multiple myeloma, where it recently completed a new share issue to finance a Proof-of-Concept study in the indication. You can read more about the study hereMultiple myeloma is an incurable hematological cancer that arises from plasma cells in the bone marrow.
The disease is similar to that of bone metastases from prostate cancer, where bone cells and tumor cells stimulate each other, leading to bone breakdown (the so-called vicious cycle). Phase II results show that OsteoDex has an inhibitory effect on the bone-degrading osteoclasts as well as a direct cytotoxic effect on tumor cells.
The company has previously conducted preclinical studies at Karolinska Institutet which shows that OsteoDex has a tumor cell killing effect also on various myeloma cell lines and that the cytotoxic effect is strong even at low concentrations.
Great potential for the technology
If the upcoming Proof-of-Concept study in multiple myeloma is successful, it will open the door to another huge treatment market for OsteoDex. It would mean having a potential drug for two major cancer indications, which would place the company in a very advantageous position in discussions with potential partners.
Despite this, it can be noted that the company has had a volatile journey on the stock market since the phase II results were presented in 2018, with a 2-year follow-up in June 2020. An excited expectation of a partner agreement has changed to impatience, which has pushed the valuation down to below SEK 200 million. This is despite the fact that you can find higher valued biotech companies elsewhere that have not come as far in their development.
DexTech's CEO on platform technology
As mentioned, DexTech is at an interesting stage, where it has a validated CDC technology and is now entering the clinical phase with the lead candidate OsteoDex in a second indication. BioStock contacted the company's CEO Anders R Holmberg to learn more about the GuaDex platform and its advantages over other treatment principles.
Your drug candidates are so-called CDCs. Could you tell us a little more about what characteristics distinguish them from other cancer treatments, such as antibody-drug conjugates (ADCs)?
– There are many factors that affect the possibilities of making CDCs and ADCs, such as conjugation chemistry, time in the blood circulation, stability, toxicity, treatment resistance, etc. Many of these are significantly more favorable for CDC development. The most important difference is that many billions of USD have been invested in ADCs, in contrast to CDCs, which are almost unexploited with a minimum of capital invested.
What makes the CDC field so unexploited compared to ADC?
– This is because the CDC examples that exist in oncology are pre-clinical. As is well known, it is a very big step to go from pre-clinical to clinical research. Ever so promising pre-clinical results always require translation into clinical results, i.e. in patients, in order to be valued. As far as I know, we are quite alone in having included CDC technology in clinical trials for the treatment of cancer patients.
Right now your focus is on mCRPC and myeloma, but how would you describe the platform's potential in other cancer indications?
– Our CDC platform is generally drawn to the so-called microenvironment of malignant tumors and also has strong tumor-toxic properties, so the possibilities are many and, as I said, unexploited.
Is there potential for GuaDex outside of oncology?
– It absolutely does, imagination and resources are the limits.
You have previously communicated that the CDC platform can also be used to improve or modify the properties of other drugs, including increasing their solubility. In what situations is this important and what does this mean for the platform's potential?
– It is well known that CDC can change and enhance the properties of the ligands that are included. Among other things, the side effects of a drug can be reduced, of which our own candidate OsteoDex is a good example. CDC's highly hydrophilic properties can also make a poorly soluble substance more water-soluble.
– Solubility is an important aspect, as ligands that may be of interest for conjugation are often poorly soluble. Here too, OsteoDex is a good example, where alendronate has limited water solubility.
The market has long been thirsty for a partnership agreement and the share price has been punished as a result. Now you are entering another indication, with all that it entails in terms of potential and risks. How do you justify this investment right now?
– It strengthens our chances of a good deal.
You just released your fourth quarter report, what milestones are you looking forward to achieving in 2022?
– Actually several important things, but perhaps mainly two things. To create the best conditions for business based on the values in our portfolio, and to get the myeloma study in place with documentation, contract, application, GMP production and so on.