NASDAQ:LEXX
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Following the rollover into the new year, Lexaria Bioscience Corporation (NASDAQ:LEXX) updated stakeholders with the final results from its human pilot study investigating the DehydraTECH (DHT) delivered GLP-1 agonist Rybelsus. As a reminder, Lexaria had previously provided preliminary data late last year for this study regarding the evaluation of the glucagon-like peptide-1 (GLP-1) agonist class formulated with DHT. The goal of the research is to determine whether or not employing DHT for delivery could reduce side effects, enhance weight loss, improve health outcomes, increase bioavailability and reduce cost relative to other methods of semaglutide delivery. Shortly after sharing the final results, the company set out a comprehensive plan to further develop DHT with GLP-1 agonists. Five additional studies are planned to support commercial partnering and commercial applicability of synthesizing GLP-1 agonists with DHT.
Human Pilot Study Final Data
Lexaria had provided preliminary data in late November with respect to the pilot study which compared 7 mg of DHT-Rybelsus versus a matching amount of drug substance in a Rybelsus tablet. Rybelsus has distinguished itself with strikingly low bioavailability of 1% or less, providing an opening for an alternative that achieves better results. The exhibit below is updated from the previously released data and illustrates final blood plasma levels of DHT-Rybelsus and Rybelsus tablets over a 10-hour period with the DHT formulation achieving higher blood levels at each measurement point. We note that compared to the initial report of the data back in November, the separation of the two curves is greater in the final report with the Rybelsus control generating slightly lower blood levels in comparison.
The separation between the DHT and Rybelsus curves was maintained for the entire 24-hour measurement period and was about 25% higher at the final hour. For the 24-hour observation period, blood levels for the DHT-Rybelsus arm averaged 15% higher than the control.
Two of the three control subjects and none of the four DehydraTECH GLP-1 subjects reported experiencing moderate nausea. All three control subjects reported experiencing mild nausea at both the 2-hour and 10-hour timepoints whereas only one DehydraTECH semaglutide subject reported mild nausea and only at the single, 2-hour timepoint.
Updated data for blood glucose levels was also provided in the final results for the pilot study. Compared with the first report, both curves were generally lower than before. The final results demonstrated lower overall blood glucose levels and less variability for the DHT-Rybelsus formulation compared with Rybelsus tablets. The study evaluated blood glucose levels every 20 minutes for the first few hours then every hour over the measurement period. Subjects consumed a standardized meal at the 240-minute (4 hour) mark and a snack at the 360-minute (6 hour) mark. As can be observed in the following exhibit, the spike in blood glucose levels for the DHT-Rybelsus subjects was less pronounced than that for the Rybelsus tablet group following the meal at the 240 minute mark.
The semaglutide study is intended to provide pharmacokinetic and pharmacodynamic data to help guide future work. Since there were only seven subjects in the trial, there are insufficient data to provide significant results; however, as shown in the information provided, initial indications show improved performance from the DehydraTECH formulations. Study investigators surmised that the improved delivery of DHT-Rybelsus is most likely responsible for the observed greater efficacy in achieving sustained blood glucose reduction, which also suppressed the after-meal spikes in blood glucose produced by the control group.
Lexaria used crushed Rybelsus tablets as source material for its DHT formulated product, which combined two delivery technologies that may together have had an impact on performance. Rybelsus uses the SNAC technology which is a synthetic N-acylated amino acid derivative of salicylic acid. From the first pilot study, it is unclear what effect SNAC had on the results generated by DHT-Rybelsus. Lexaria will conduct further studies with alternate formulations that may be able to determine if SNAC impacted the results. Another important element to consider is the value Novo Nordisk attributed to the technology. The Danish company acquired Emisphere and its royalty obligations for $1.8 billion in 2020. While it is too early to determine the capabilities of DHT-delivered semaglutide, this transaction gives some idea of what even a weakly effective delivery system could be worth to a large pharmaceutical company.
2024 GLP-1 Agonist Study Program
Following the report of final data for the DHT-Rybelsus comparison study, Lexaria outlined an extensive research and development program for 2024 in a January 16th press release. The goal of the work is to further characterize the pharmacokinetics of DHT-semaglutide delivery. Additionally, the company seeks to identify the commercial applicability of DHT-formulated versions of semaglutide, liraglutide and tirzepatide. With this end in mind, Lexaria has planned one animal and three human studies along with long-term stability testing of DHT compositions of GLP-1 agonists. All of the proposed studies are dependent upon availability of sufficient funding. All human studies will be investigator-initiated, non-registrational studies and will require certain approvals before beginning. Third-party laboratories will be used exclusively.
Chronic Dosing Animal Study
A chronic dosing animal study that will advance 12 arms with 8 to 10 obese rats per arm is being readied for Spring 2024. It is planned to run for 12 weeks to evaluate weight loss, pharmacokinetics and blood sugar control over the duration of the study. Following collection of the data, full analysis will be performed and results will be shared with stakeholders. DHT formulations of semaglutide and liraglutide, alone and together with DHT-CBD, will be evaluated. This study will incorporate both the synthetic N-acylated amino acid derivative of salicylic acid (SNAC) technology developed by Emisphere and a compounded formulation of semaglutide to further evaluate the contribution of SNAC to drug delivery. A report of interim results is expected while the study is in progress.
Human Pilot Study #2
A second human pilot study is tentatively scheduled to begin in Spring 2024. Up to eight healthy volunteers will be administered a single dose of DHT-semaglutide (what we termed DHT-Rybelsus above) capsules, similar to the formulation used in the first human pilot study. An oral dissolvable DHT-semaglutide tablet will be administered to evaluate whether or not it can be effectively delivered using the sublingual/buccal tissue route. Tolerability, side effects, pharmacokinetics, and blood sugar control will also be evaluated. As with the first human pilot study, the formulation of DHT-semaglutide will use Rybelsus tablets as source material for the composition.
Human Pilot Study #3
Planned for May or June 2024, the third human pilot study will enroll up to eight healthy human volunteers. Subjects will be administered a single dose of DHT-tirzepatide, which will be compounded from Eli Lilly’s Zepbound and manufactured into capsules. Study endpoints include tolerability, pharmacokinetics and blood sugar. The trial will evaluate DHT effectiveness in combination with a dual action GLP-1 agonist and a glucose-dependent insulintropic peptide (GIP) drug absent the SNAC formulation used in the Rybelsus semaglutide composition from the first two human pilot studies.
Chronic Dosing Human Study
Planned for 3Q:24, a 70-90 subject human study in pre-diabetic and Type 2 diabetic individuals will dose daily using DHT-CBD and DHT-Rybelsus capsules. It will evaluate tolerability, pharmacokinetics, weight loss and blood sugar among other metrics over a 12-week period. The study seeks to compare the performance of DHT-CBD product with DHT-Rybelsus product both separately and together relative to a placebo arm. A secondary goal for the study is to confirm glycemic control and weight loss shown in the first pilot human study.
Long Term Stability Testing
Lexaria also plans to evaluate the chemical and microbiological purity and stability of select DHT compositions over an extended period of 6 to 12 months. Long-term stability is a necessary feature if the DHT-formulations are to be commercially successful and replace injectable versions of GLP-1 agonists. Success in this study will support this objective.
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1. Source: Lexaria Press Release, January 4, 2024. This was a small sample with only three observations for Rybelsus and four for DehydraTECH.
2. Source: Lexaria Press Release, January 4, 2024. This was a small sample with only three observations for Rybelsus and four for DehydraTECH.
