Update Compendium 2023

Update 4: 17 April 2023

 Presentation at the 22nd Annual Needham Virtual Healthcare Conference 2023 & Timeline Expectation Updates

Bottom-line Up Front (BLUF): Overall I was impressed by Dr. Missling's breadth of material and exhaustive summary of the companies current stage. Within this report you will find presentation of key-items including gender-specific disease onset, expectations for AD 2b/3 data, drug-to-indication cost methodology, and more. 

Presentation Key-Items:

My Updated Timeline Projections for 2023

These are my personal projections and trading should not be conducted based on these timelines. Changes are in blue.

Assessment: A clear standout from today's presentation was Dr. Missling's clear proclamation regarding the AD 2b/3s unprecedented cognitive & activities of daily living results. Additionally, we found specific mention of multiple biomarkers (in addition to S1R) to be extremely interesting. Direct mention of CDK5 is especially exciting, as we had previously featured the protein in one of our videos  (starting at 8:40 min). Furthermore, Dr. Missling hinted multiple times to the closeness of full AD data release. Based on his exact comments, we assess there will be a PR with more AD data (partial) before a peer-review publication as the company wants to begin conversations with regulators and possibly wishes to circumvent some of the bureaucratic time constraints that would come with waiting for a peer-reviewed publication. We also assess that Anavex is keenly interested in presenting gender-specific addendum to their regulatory package. This is a unique approach as women's health is commonly neglected in CNS study.

 Other key takeaways include ALS as a likely indication, possible adjunctive therapy testing with Lecambi (certainly little granularity here), dusting off Anavex-1066, and explanation as to how different pricing can occur between rare disorders and common large-population CNS disorders. Dr. Missling hit home numerous times the companies emergence as a commercial-stage company. With full Alzheimer's data and Rett trial suite data expected shortly (EOY), it is likely discussions with regulators will begin towards global commercialization for at least Alzheimer's by the end of 2023. Considering Dr. Missling's commentary on biomarker use, efficacy, administration, and safety, the company clearly has high expectation for subsequent approval.

Update 3: 30 March 2023

 PDD OLE Preliminary Data Commentary 

Bottom-line Up Front (BLUF): Despite COVID-19 disruptions to OLE enrollment, a small patient cohort was able to show clinical benefit in all measured efficacy endpoints at 48 weeks following a substantial (41 week average) unintended washout period being referred to as a 'drug holiday'. The drug holiday caused patients to regress from the therapeutic progress made by the end of the primary trial period (14 weeks). 

COVID-19 in Spain and Trial Relevance: Spain was one of the hardest hit European nations from 2020 - 2021 by COVID-19. Not only did the country have the highest incidence (only surpassed by Russia), Spain also had one of the most under-budgeted healthcare infrastructures - 5.9% lower than European standard. The Anavex PDD primary trial coincided with a State of Emergency announcement on 1 Oct 2020 which ultimately precluded non-essential medical care (Figure 1).

Figure 1. Spanish COVID-19 Data with Timeline

COVID-19 in Spain and Trial Relevance Continued: The preponderance of Anavex's Spanish clinical sites were located in high-infection areas, especially those within the 'Madrid pocket'. This surely had a high impact on patient ability to continue the OLE trial, even after the State of Emergency ended, as the nation exceeded hospital capacities in 80% of responsive medical care facilities for an extended period of time (Figure 2.).

Figure 2. Anavex PDD Trial Sites in Spain with COVID-19 Infection Rates

COVID-19 in Spain and Trial Relevance Summary: Due to prolific COVID-19 infection and overwhelmed (and underfunded) healthcare facilities, Anavex PDD patients had little opportunity to continue the OLE. This inaccessibility likely continued past the end of the State of Emergency on 9 May 2021 as local quarantine laws and hospitalization in high-risk zones continued through 2021. Due to COVID-19, enrollment in the OLE was extremely low (N=20 at 48 week) and efficacy in the following section should be viewed cautiously. 

PDD OLE Preliminary Data: All of Anavex's clinical outcomes saw positive trend, especially in MDS-UPDRS Part 3, RSBDQ, and CGI-I.

Figure 3. All Available Mean OLE Data Calculated by SOTC Analytics [Mean Scores are Considered More Complete as they Have Higher Weight Towards Outliers - Whole Patient Population]

Figure 4. All Available Median OLE Data Calculated by SOTC Analytics [Median Scores Put More Emphasis on 'the Average Patient' by Reducing Outlier Emphasis; Not as Commonly Used as Mean Score as Considered Less Complete]

Post-Edit Inclusion of Median Scores (Figure 4.): After conversations with board-poster 'Georgejjl', I decided to include a supplementary median data graphic. Viewers should consider mean data (Figure 3.) as more complete data as it equally weighs outliers and 'average patients'. Median data negates/reduces outlier emphasis (super responders and under-performers), so visualization of median data still plays a role as it displays a more 'average patient' response.

PDD OLE Preliminary Data Main Findings:

PDD OLE Preliminary Data Bottomline: Despite a small enrollment, Anavex was able to see continued positive trends in all trial endpoints. We are most pleased with MDS-UPDRS Part 3, RSBDQ, and CGI-I. It is pleasing to see continued benefit in the MDS-UPDRS Part 2 + 3 as it foretells potential benefit in some of Anavex's rare/pediatric indications featuring movement disorders, sleep disruption, behavioral problems, and self sufficiency inabilities. Ultimately, we are pleased with the preliminary OLE data. While it is certainly not what we had hoped for in terms of size and execution, positive trends will still likely be used towards various data packages. We noticed in the 30 Mar 2023 PR the mention of the upcoming/expected PD pivotal trial. Interestingly, the company did not make mention of a pivotal trial for Parkinson's disease dementia and we are unsure if that was because of its 'implied' nature or if the company is potentially pursuing accelerated approval pathways. We have no official position on this matter but we found it interesting nonetheless.

Finally, while we are pleased with today's data outcome, we drafted an email to Anavex to express perturbation over the companies willingness to keep investors abreast of important developments in their clinical trials. Specifically, we are displeased that the company did not relay to investors earlier that most PDD patients were unable to continue in the OLE. Additionally, we felt that this data - while preliminary, was incomplete and partially unclear - and we expect better communication (especially if written) at this stage in development. 

SOTC Analytics looks forward to Anavex's next milestones, which we believe will be full AD topline data (in PR or conference) and/or partnership. As macroeconomics continue to deteriorate, we are unsure how this may influence Anavex's ability or willingness to accept certain commercialization partnerships with large (or medium-sized) pharma. Anavex has a good cash position which will prevent them from accepting a low offer - which is more likely as market conditions worsen and valuations drop. It may actually be more benefical to partner with a medium-sized pharma and form a true 'partnership'. We look forward to seeing which route Anavex will take towards this goal.

Update 2: 12 February 2023

 Dr. Timo Grimmer Interview Final Thoughts & Expectations for 2023

Bottom-line Up Front (BLUF): It is my belief that Dr. Grimmer was likely shown raw scores post-management CC in Dec 2022 which spurred on his acceptance as Scientific Advisor for the company and increased enthusiasm during our interview. While I want viewers to form their own opinion after watching the interview (below), my key takeaways are as follows:

My Timeline Projections for 2023

As the company approaches commercialization, there are a number of key milestones I am anticipating this year. These are my personal projections and trading should not be conducted based on these timelines.

Assessment: SOTC Analytics assesses 2023 as probably the most important year Anavex will have as a company. We are expecting partnerships, commercialization (or definitive notion towards beginning commercialization), and the completion of Anavex's Rett Syndrome trial suite. Considering recent influxes in investment by funds and institutional investors, as well as key developmental milestones expected, we believe the proverbial launch-pad has been set and this year likely represents the final opportunity to accumulate at discount. 

Update 1: 11 February 2023

Lecanemab & Blarcamesine: Comparing CDR-SB & Clinically Meaningful Decline Thresholds

Blarcamesine Features Dramatically Improved CDR-SB Scores Over Lecanemab When Taking Into Account Disease Stage

Bottom-line Up Front (BLUF): After carefully examining documented thresholds for CDR-SB clinically meaningful improvements and decline, SOTC Analytics came to new conclusions that we believe have not been discussed by any other source to date. Previously mentioned by Anavex, Blarcamesine garnered faster response over Lecanemab. In fact, Blarcamesine attained the same response as Lecanemab but 24 weeks earlier. That is extremely interesting considering disease-stage of enrolled patients in each trial. The Lecanemab CLARITY trial featured significantly less impaired patients (25.6 MMSE) over the Blarcamesine 2b/3 (23.57 MMSE). When considering published clinically meaningful thresholds for CDR-SB, we can come to the conclusion that Blarcamesine was 125% more efficacious than Lecanemab in CDR-SB when it comes to decreasing patient proximity to clinically meaningful worsening (decline) when considering disease stage. In other words - Blarcamesine-dosed patients at the ~1 year mark demonstrated a far greater distance from what is considered to be meaningful decline than Lecanemab. Clinically meaningful status - both improvement & worsening - are thresholds established by clinicians to indicate when a treatment or disease progression begins noticeably effecting a patient for the better or worse. More information is available below. Note: Although it is known that CDR-SB is limited in its ability to consistently detect a treatment effect in clinical trials, todays findings are still extremely interesting as Anavex continues to compare efficacy against competitors whom used CDR-SB and amyloid reduction to garner approval by the FDA.