It will certainly be interesting what BOT prioritises for...

It will certainly be interesting what BOT prioritises for development after Sofdra. Personally, I think it'll be 1801 over acne (1503) given its QIDP status (faster regulatory pathway and an extra 5 years of exclusivity against generics is valuable), increasingly urgent medical need, less competitive landscape and likely quicker path to market. No doubt they'll be expensive (perhaps one more than the other), but there should be significant operating cashflow generated from Sofdra to fund, so maybe no more dilution. That is, unless there's more near term lower hanging fruit bolt on acquisitions first like Vince mentioned in the latest webinar? Should be an exciting time to hold and watch it play out.

By niche I mean it has its own value proposition (more effective, safer and/or easier to use/access) that warrants further investigation and possibly full commercialisation. Excuse the long post, but I want it to be ultra clear - 1801's efficacy via its method of action and use case is its niche.

1i. 1801 Method of Action:
(a) Cell membrane disruption - CBD has broad properties (lipophilic/fat loving) that enable it to integrate into, and disrupt, bacterial cell membranes (their otherwise orderly arrangement of lipids), impacting the cell's integrity (leakage of essential ions and molecules), leading to cell death (cannot perform essential functions like energy production, nutrient transfer and waste elimination).
(b) Inhibition of biofilm formation - similarly, CBD can disrupt bacteria's existing, and interfere with the formation of new, biofilm, which are layers/shields created to protect against external threats. By disrupting biofilm, the bacteria is exposed to the body's immune response and/or other antimicrobial agents.
As you can see, this is a non-specific method of action, that that does not rely on targeting select bacterial functions or pathways. This means the bacteria doesn't have a single point to mutate against, making it significantly harder to develop resistance.

1ii. 327 Method of Action:
(a) Cell wall disruption - 327's polymer specific structure is designed to specifically target the bacterial cell walls and their specific function of synthesis/building, which involves attacking specific components such as peptidoglycan, compromising the cell wall's integrity, leading to cell death.
(b) Induction of oxidative stress - 327 generates reactive oxygen species (ROS), which directly target and damage bacterial DNA, proteins and lipids, leading to cell death.
Interestingly, 327 is designed with a self-perpetuating bactericidal effect, which means it continues to act against bacteria over time, ensuring sustained antibacterial activity for longer - this is unique and buys time. However despite this effect, it doesn't change the fact that 327 employs a specific method of action because it focuses on well-defined bacterial targets - the cell wall synthesis pathways and the generation of oxidative stress. This means that bacteria can more easily develop resistance by (1) modifying enzymes, (2) altering pathways involved in cell wall synthesis, (3) preventing/blocking the antibiotic from reaching its target, or (4) enhancing their antioxidant defenses, which are all well documented challenges in antibiotic therapy.

2. Use Case: as mentioned before, these differences in action methods make 327 more prone to resistance development over time and hence more suitable for non-preventative uses. This means 327 is best reserved for strategic and limited use to treat active infections. In contrast, 1801's broad, non-specific action make it more suitable for preventative or ongoing use, such as in the management of chronic or recurrent infections, wound care or as a topical agent to prevent bacterial colonisation, without the same risk level of resistance development.

R435 has a similar to 327 specific method of action (targeting cell walls and ROS mechanism). R529 targets viruses - a lack of understanding of the difference between bacteria vs virus is partly to blame for the growing AMR crisis, but hey it's relatively cheap and easy to walk out of the Doc's office with a antibiotic prescription that helps you feel safe and protected. Overcoming the AMR threat will require more than antimicrobials, but a cultural shift in how we perceive and use medications.

To summarise, both 327 and 1801 have their own distinct and valuable roles in development, and I wish both companies and their holders success in solving unmet medical needs and securing the bag 8)

Note all of the above requires more research to confirm, hence their clinical stages.