Update 8: 4 Oct 2023 Dr. Marwan Sabbagh, Chairman of the Scientific Advisory Board Bottom-line Up Front (BLUF): On 12 Sep 2023 it was announced that Dr. Marwan Sabbagh, a behavioral neurologist in the Alzheimer's and Memory Disorders Program at Barrow Neurological Institute joined the Anavex team as Chairman of the Scientific Advisory Board. He is the Vice Chair of Research in the Institutes Department of Neurology. A look at Dr. Sabbagh's recent peer-reviewed journal work points to an exceptional repertoire of skills useful to Anavex and their precision medicine approach, with keen focus on differentiating various types of CNS disorders via clinical assay and biomarkers, and how co-morbidities play into severity, progression, and treatment. Here are some of his latest works and commentary:
ATN cerebrospinal fluid biomarkers in dementia with Lewy bodies: Initial results from the United States Dementia with Lewy Bodies Consortium
Type 2 Diabetes Comorbidity and Cognitive Decline in Patients with Alzheimer's Disease
Listening session with the US Food and Drug Administration, Lewy Body Dementia Association, and an expert panel
Integration of canonical biomarkers in the diagnosis of preclinical Alzheimer disease
Effect of ApoE isoforms on mitochondria in Alzheimer disease
APOE e4/e4 homozygotes with early Alzheimer's disease show accelerated hippocampal atrophy and cortical thinning that correlates with cognitive decline
Independent Interview with Deborah Kan and Dr. Sabbagh on CNS Disorders, FTD, Biomarkers, and Mis-diagnosis [Link]
As mentioned, Dr. Sabbagh recently joined Anavex as inaugural Head of the Scientific Advisory Board. After watching three hours of his lectures and reading through about 15 articles co-written by Dr. Sabbagh, it is clear that Anavex found an absolute honcho in the biomarker and diagnostic space. Listening to him speak, it is certain that he has garnered expertise rarely seen in the field, and has access to vast clinical resources including databases, most clinical assays, (blood, MRI, CSF, PET) and laboratories that are not normally at the immediate disposal to most doctors/researchers. Beyond this, Dr. Sabbagh carries himself with utmost professionalism, pride, and ambitious gusto. His intelligence and awareness in ongoing CNS research is obvious and definitely has my attention.
During the interview linked above, he points out that only 1/3 of CNS patients have a pure disease. Only 1/3 of Alzheimer’s patients have plaques and tangles and nothing else. The other 2/3 of patients have a-synuclein or vascular disease, immune disorder and otherwise. Most CNS disorders converge in some manner with variation in disease progression and severity dependent on the combination and genetic makeup. This is an important metric and underlies significant inabilities for primary care providers to accurately and consistently diagnosis dementias. Further evidence of this can be found in this article on Lewy Bodies, which was extremally insightful. Within, it is stated that up to 11.1% of patients showing amyloid and tau pathologies also have Lewy Bodies. Conversely, 22.4% of patients had no amyloid, tau, or Lewy Bodies at all (Fig 1 in article). This is important because patients with Alzheimer's disease and Lewy Bodies consistently scored lower on clinical performance tests compared to dementia patients without Lewy Bodies, and patients without both Alzheimer's pathologies and Lewy Bodies scored higher on average (Fig 2 in article). Additionally, the rate of cognitive decline was significantly altered in Alzheimer's patients with Lewy Bodies (Fig 3 in article), and it's a big difference. Combination of co-morbidities and disease pathologies matter to a clinical trial outcome and therapeutic effect of a drug candidate.
Anavex is looking to be the leader in CNS precision medicine, we know this.
16 Mar 2021 PR: ‘“This paper highlights the relevance of the analyses of gene expression data in precision medicine to drug development that may predict increased chances of success of Alzheimer’s disease treatments, which is especially relevant in late-stage clinical studies like the ongoing ANAVEX®2-73 Phase 2b/3 clinical Alzheimer's disease study,’ said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex.” - 16 Mar 2021 PR
Furthermore, as stated in the AAIC 22 PR from 31 Jul 2022, Anavex was one of the first to run a genomic analysis of a now-definitively disease-modifying compound in Alzheimer’s disease and Parkinson’s disease dementia. Dr. Missling, Ariana Pharma, and staff found a myriad of genes that were improved upon taking the drug. These genes were primarily related to protein clearing, mitochondrial health, and apoptosis (cell death); although, there were many other genes identified with implications in vascular health, neuronal networking, mRNA stability, amyloid processing, and many more. “These findings will facilitate contextualization of upcoming readout of ANAVEX®2-73 Phase 2b/3 Alzheimer’s disease clinical trial”.
So how does this tie into Dr. Sabbagh? After reviewing his work, it is easy to conclude that Anavex chose an expert in the diagnostics and biomarker field to come in and help contextualize disease combination, co-morbidities, and genomic sequencing for their Alzheimer's trial. Being able to fully distinguish responders to non-responders is next generation precision medicine that has not been fully possible up until the last few years. As blood diagnostics, emerging genomic research, and understanding of disease effect become more available, other companies will be able to follow the path Anavex currently trailblazes in CNS precision medicine.
Assessment: Post-trial, Anavex needed an in-house statistician, and fast. A few months later, it was announced that the company hired the FDA's former Lead Neurology Statistician as Vice President, Head of Biostatistics. Dr. Kun Jin was an impressive hire to be sure. Waiting until after the trial ended before hiring a statistician was certainly an oversight; but what the company lacks in timeliness, they absolutely make up in quality. The hiring of Dr. Sabbagh is a very similar situation. Anavex once again brought in an extremely qualified specialist to fit a need the company has to excel their lead compound through approval and into patient hands. In this case, it is almost certain that Dr. Sabbagh was brought in specifically to help contextualize patient pathologies and genomics to therapeutic effect. Having met and spoke with Dr. Sabbagh in-person at AAIC 23, I can say with utmost confidence that his expert guidance in this endeavor will be some of the best in the industry. It is likely that Anavex's full scientific release will include detailed precision medicine unseen before in the CNS-space. If you'd like to listen to more of Dr. Sabbagh, here is another interview that I believe shows off the kind of confidence and expertise he brings to Anavex.
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