Tradipitant is a neurokinin receptor 1 (Also called tachykinin receptor 1: Tac1R or substance P receptor: SPR) antagonist, meaning that it blocks/prevents neurokinin receptor 1 (NK1R) from functioning.
Motion sickness is probably something you are already familiar with so I wont bother explaining it. Gastroparesis is a condition where your intestines are not able to function properly, leaving bits of food stuck inside your digestive system. This gives rise to unpleasant feelings of bloatedness and nausea, as your body struggles to break down the food and move it along the intestines.
An aside on NK1R
NK1R has been an interesting target, both from a commercial and personal standpoint since my research has crossed path with this receptor numerous times.
In general it has been associated with conditions that broadly relate to pain, both external pains such as heat or injury, as well as internal pains from organs (Such as feelings of nausea).
An aside on NK1R expressing populations in the brain and gut
NK1R is expressed in a variety of places, with the contribution of NK1R from different parts of the body mediating different aspects of pain/nausea still a field of active research.
So far, it has been shown that NK1R in the spinal cord of mice, was able to mediate various types of external pains, such as painful heat, tail pinches or foot shocks
[Barik, A., Sathyamurthy, A., Thompson, J., Seltzer, M., Levine, A., & Chesler, A. (2021). A spinoparabrachial circuit defined by Tacr1 expression drives pain. Elife, 10, e61135.Barik, A., Sathyamurthy, A., Thompson, J., Seltzer, M., Levine, A., & Chesler, A. (2021). A spinoparabrachial circuit defined by Tacr1 expression drives pain. Elife, 10, e61135.];
a similar role for NK1R neurons in the parabrachial nucleus has also been shown.
[Deng, J., Zhou, H., Lin, J. K., Shen, Z. X., Chen, W. Z., Wang, L. H., ... & Sun, Y. G. (2020). The parabrachial nucleus directly channels spinal nociceptive signals to the intralaminar thalamic nuclei, but not the amygdala. Neuron, 107(5), 909-923.]
A bit more relevant to the drug and condition being targeted by VNDA are the NK1R neurons in the DVC (Dorsal vagal complex), a small brain region near the backside of the brainstem that is involved in many internal bodily processes (Such as regulating your breathing, gut motility, blood pressure etc…). Tac1 neurons (The neurons that provide the ligand for NK1R; you can think of Tac1 as the bodies natural drug for activating NK1R) are able to drive nausea/retching behaviours in mice.
[Xie, Z., Zhang, X., Zhao, M., Huo, L., Huang, M., Li, D., ... & Cao, P. (2022). The gut-to-brain axis for toxin-induced defensive responses. Cell, 185(23), 4298-4316.]
Furthermore, direct infusion of Tac into the DVC is capable of decreasing intragastric pressure, which may contribute to hindering digestive processes.
Finally within the gut itself, enteroendocrine cells also express NK1R, and are able to drive conditioned taste avoidance in mice (A way of measuring nausea in mice).
[Bai, L., Sivakumar, N., Yu, S., Mesgarzadeh, S., Ding, T., Ly, T., ... & Knight, Z. A. (2022). Enteroendocrine cell types that drive food reward and aversion. Elife, 11, e74964.]
The TL;DR is that while our knowledge on NK1R expressing populations is not complete, the general tendency is for the NK1R to be involved in various sensations that we may deem unpleasant, whether that be pain or nausea.
The strategy
Given these general effects of NK1R, the strategy for VNDA 0.00%↑ is essentially to block NK1R, to prevent these effects from occurring. In one aspect, it is unique in being a peptide receptor antagonist to treat various interesting conditions. Motion-sickness can be treated with various drugs, such as broad dopaminergic antagonists, muscarinic antagonists or Htr3a antagonists, but dopaminergic, cholinergic and serotonergic signalling are so ubiquitous and used over many types of processes, outside of pain and nausea, that it inevitably gives rise a plethora of unwanted side-effects, that are only warranted/acceptable in patients where the treatment of nausea outweighs those negative side effects; unreasonable for treating everyday motion sickness. Scopolamine is a muscarainic antagonist that is indeed used for preventing motion-sickness, but being a cholinergic drug (cholinergic systems are implicated in many processes, notably parasympathetic autonomic systems), leads to side effects of dry mouth, dizziness and fatigue.
NK1R is unique in being almost only implicated in processes of pain and nausea, which raises the possibility of being able to sidestep a lot of the side effects that other drugs have.
In fact, an FDA-approved NK1R antagonist already exists, Emend/Aprepitant; which is used specifically for preventing CINV (Chemotherapy-induced nausea and vomiting) and PINV (Postoperative nausea and vomiting). It has a remarkable side-effect profile; that is barely any of notable severity.
VNDA is simply re-equipping the same strategy for use in everyday motion-sickness and gastroparesis.
Clinical data
In a double-blinded placebo-controlled study, although a bit too qualitative in analysis for my tastes, some leeway is expected since they just got people to just ride boats out in the ocean and assessed the rate of vomiting; ocean choppiness can't be controlled by the experimenter (The degree of chopiness was quantified for each boat, such as peak wave height, wave period and average wind speed; but subsequent analyses simply grouped conditions into calm and rough, based on a peak wave height of 1m as a threshold. Some kind of regressive method between peak wave height and incidence of vomiting, and comparing slopes between the placebo and tradipitant group would have been more satisfying, but maybe Im just being pedantic…)
Incidence of vomiting decreased dramiatcally, from 72.2% in placebo patients down to 15.8% in patients who took Tradipitant orally (170 mg) 1 hour before getting on the boat. Qualitative assessments of motion sickness (MSSS, a 7 point scale, from 0 to 6) were lower too, decreasing from 4.57 to 3.19.
Effect is much milder for calmer seas (Defined as <1m wave height), showing a decrease from 26.&% to 18.2%; whereas the MSSS was unchanged.
[https://doi.org/10.3389/fneur.2020.563373]
In a double-blinded study for gastroparesis; here again, many measures are based on qualitative subjective scales, but in tandem with objective measures such as percentage of nausea free days and decrease in vomiting frequency show a consistent picture in decreasing the severity and frequency of nausea and vomiting and feeling of bloating.
[https://doi.org/10.1053/j.gastro.2020.07.029]
More phase 3 clinical data is expected for the motion-sickness study and a New Drug Application (NDA) to the FDA for the use of Tradipitant in gastroparesis is expected later sometime in the middle of the year.
VNDA 0.00%↑ has many other drug products and again, I’m not familiar with the financials or governance enough to take a long-term position. Here again, the idea would be to inventory stock (In most likelihood, starting tomorrow at market open) and sell into any news from additional clinical data, which I expect to be positive. Since the company does have other drug products, this makes inventorying stock a bit more trickier, since news from other drugs can interfere with the trade; which I will probably just try to adjust to by reducing position sizing a bit.
For anyone with a longer term view or willing to do more financial/governance research and find it to be acceptable, they may be more inclined to hold it all the way through until an NDA for Tradipitant is approved for gastroparesis (Or take a loss if it ends up being rejected; I still dont consider myself astute enough to predict how the FDA is likely to respond, still something I’m trying to get a better handle of).
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.
By “middle of the year” are you referring to this year or next?