Replies to post #251077 on Biotech Values

[dewophile]

You may be able to combine oral small molecule drugs with oral peptide drugs to drive efficacy closer to that of injectables. That would make both classes of oral drugs bigger winners at the expense of the injectables.

[Mufaso]

Dew- I agree in general with the comments you made but am reserving judgement on your conclusion that ALL oral peptide weight loss drugs will be marginal players.

My comments include:

• oral drug delivery methods are continuing to evolve
  
• fasting requirements of a peptide based formulation are a disadvantage but not a big deal for most if the pill is once daily taken first thing in the morning and fasting period is about the time it takes you to shower. I simply disagree that this becomes much of an issue if the drug has other benefits like being more tolerable.
  
• there are other attributes besides weight loss that this class of drugs is thought to be useful for. You may not need or want the large dose in a maintenance setting, or you may be targeting something in addition to weight loss such as NASH, MACE, and other indications that a multi agonist peptide/ might be useful for.
  
• VK2735 provides a special case as an oral as VK2735 is likely to be successful as an injectable. Following it with the same drug as an ORAL in maintenance mode has an appeal. Additionally, if it can be proven to work as an oral, an all oral combination with VK2809 for NASH is also appealing as we have discussed before.

For peptide based obesity NME's - I believe you are thinking about VKTX's VK2735 and NVO's amycretin. Regarding amycretin it is using same technology used in its oral formulation of Rybellsus so it is not ideal.

This article seems to suggest there are multiple ways (besides carriers that peptides can enter the bloodstream:

Current Evidence on the Bioavailability of Food Bioactive Peptides
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582556/

However, in the last few years, it has been found that many peptides are absorbed by intestinal cells under normal conditions, being detected in both newborn and adults’ bloodstream and/or target organs where they exert their biological activities [83,84,85].

To date, four different routes of peptides absorption have been described: paracellular diffusion, transcellular passive diffusion, transcytosis, and carrier-mediated transport.

Do you (or anyone else) have any comments on what Viking might be doing here?

Viking has yet to disclose what method they are using in its ORAL formulation to help it make it to the bloodstream or much of anything on its molecular structure.

Right now, I think we need more data on the two large peptide molecules. NVO's body language of not advancing immediately to phase 2 on amycretin makes me think it will be as you say a marginal player at best. On VK2735, Viking prioritized that as an oral trial over a number of other things they could have done so I really want to see more data on that. It may be phase 2 before we know whether oral VK2735 can be a significant player (or if VK2735 has some unique property that makes it able to make it into the bloodstream in effective quantity.

[Mufaso]

Small molecules also have their disadvantages vs peptides such as lower selectivity and side effects.