GRTX - Avasopasem

As an adjunct for IMRT/chemotherapy to reduce severe oral mucositis

Now that I’ve started a Substack, my aim is to use it almost as a personal research diary to jot down and organise research on companies/drugs that I find interesting. Although typically I wouldn’t write like this (Less jargon, complete sentences), for the benefit of any potential readers, I’ve tried to include explanations and simplify things to make it easier to follow. Typically, I will focus on smaller cap companies, with lower float, since as a retail-punter, I have no interest in trying to compete with larger pools of capital.

Avasopasem (GC4419) is a drug, that acts as a superoxide dismutase, being developed by Galera Therapeutics GRTX 0.00%↑ for use in severe oral mucositis.

Severe oral mucositis, as its name suggests, is a condition where the mucosal barrier inside the mouth has broken down and undergone inflammation, but on a really severe level (You can think of it as an ulcer on steroids if that helps).
This is a common condition in people undergoing radiation therapy for cancer. On a superficial level, this means that patients have even more pain and discomfort on top of whatever radiation/chemotherapy induced side-effects they have, but on a more sinister level, it means that patients are not able to drink, eat or talk properly due to the sheer pain. To crown it off, it also increases the risk of infection inside the mouth

An aside on oral mucosa

Your mouth is host to a wide range of bacteria, virus and fungi, which are entering every time you breathe, eat or drink. In normal people, the mucosal layer in your mouth, which acts as both a physical and chemical barrier against these potential harms, blocks and clears them, preventing infection (Think of it as the walls around the city, preventing invaders from getting in). People with severe oral mucositis have had the integrity of their mucosal layer impaired, meaning that bacteria are able to seep in through the cracks and cause harm.

In the hospital, this leads to increased cost and labour; having to provide pain management, preemptive treatment or outright treatment of infections and nutritional/fluid replacement if the patient isn’t able to eat/drink properly.

An aside on radiation therapy

The principle of radiation + chemotherapy is to damage your DNA/prevent DNA from replicating. Cells that are most susceptible to this kind of harm are cells that divide very fast; cancer cells are a prime example of cells that are dividing, very fast.
Although radiation + chemotherapy can thus be used to kill off cancer cells, the obvious downside is that you will end up killing other cells that are dividing fast, that are not necessarily cancerous. These include, but are not limited to, hair cells (hence hair loss), bone marrow cells and skin cells (particularly thin ones with a mucosal layer, such as inside your mouth and inside your gastrointestinal tract, which is why you typically get oral mucositis and nausea/stomach pains as side-effects too).

Mechanism

Part of the reason why the inflammation begins to kick in is due to the release of free radicals. Free radicals are basically just molecules that can cause damage to things in your cell, due to unstable electrons which make them likely to react with other molecules (If that went over your head, just think free radicals = harmful).
Normal cells have the ability to clear free radicals with special enzymes which act as antioxidants (molecules that clear out free radicals), such as catalases, glutathione peroxidases, and more relevant for this post, superoxide dismutases (I notice that it is also somewhat of a fad in the US towards consuming food with supposed “antioxidant” properties. I won’t go into a rant here, but it suffices to say, there is a lot of BS-advertisement being peddled around IMO).

By using superoxide dismutases before, throughout and after radiation/chemotherapy in cancer patients, the goal is to reduce severe oral mucositis in patients.

Clinical data

So far phase 2b data shows that it works like a charm, intravenous administration of Avasopasem reduces the frequency and severeness of oral mucositis in patients, while maintaining a fairly safe side effect profile. Some common TEAE (Treatment-Emergent Adverse Effects; think of them as side effects seen after given a drug) included nausea and vomiting, which were slightly elevated over placebo. One has to caveat though, that nausea and vomiting is a common side effect in cancer patients undergoing radiation/chemotherapy regardless, meaning that its difficult to put too much attribution to Avasopasem in this case.

Phase 3 results show more or less the same trend: the rate at which severe oral mucositis is seen is slightly decreased in Avasopasem-treated patients over the entire course of radiation therapy (Albeit only slightly), but greatly reducing the duration of severe oral mucositis (from a median of 18 days on placebo, to 8 days on Avasopasem) and decreasing the overall severity of oral mucositis (27% less patients developing grade 4 oral mucositis when on Avasopasem). Further improvements are seen when using higher dosages of the drug (Up to 90 mg)

While therapies for cancer will get better and cheaper over time, radiation is still a staple for treating cancers such as head and neck cancers. It is a rather niche area, but it would seem that Avasopasem has the potential to become a standard adjunct with radiation therapy, given that there are no other FDA approved drugs to preemptively reduce the occurrence/severity of severe oral mucositis.

The FDA decision for PDUFA (Prescription Drug User Fee Act) is set to come out in early August (August 9th I believe). Given that I personally have no confidence in valuing or financially analysing stocks, my preferred trade expression is to slowly build a long position as I get closer to the FDA decision date, and then sell all after the announcement (What I like to term “Smash and grab”). Given that the only thing I have confidence is the outcome of the FDA decision, rather than the long term prospects of the company, this approach helps me mitigate having inventory risk.


Perfunctory disclaimer:
I am not a finance professional. I am a clueless retail-punter. Sometimes I will get trades right, sometimes I will get them wrong. If you ever want to actually make money from anything I say, the sure-fire method is to follow my trade when I’m right and inverse me when I’m wrong.