On April 26th, MSQ Ventures and BioAroundWorld co-hosted the MSQ CEO Webinar Series which featured Dr. Christopher Missling, PhD, the President and CEO of Anavex Life Sciences. Dr. Missling presented on “Developing Differentiated Therapeutics Improving Overall Quality of Life for People Living with Neurodegenerative and Neurodevelopmental Disorders".  
   
Dr. Missling provided valuable insights into Anavex's clinical pipeline, discussing its unique value proposition and distinguishing characteristics. He also touched upon upcoming catalysts and milestones, as well as potential opportunities for strategic partnerships and investments. This was an excellent opportunity to learn from one of the industry's leading experts on the development of therapeutics for individuals with neurodegenerative and neurodevelopmental disorders.   

Insights on Achieving a Successful Journey 

Question: Can you highlight the three most important things that made your journey a success? 

Answer: The three most important things are knowing the right people, bringing in the right people, and having a compound that shows resilience and changes the lives of patients. Finding the right people is challenging, but networking and cultivating relationships can help.  

Overcoming Challenges in Drug Development: Leveraging External Resources for Progress 

Question: What were the challenges faced in drug development and how did the team overcome them? 

Answer: Limited resources at the start of the project were overcome by accessing foundations in respective disease fields, such as the Michael Fox Foundation for Parkinson disease, the Rec Foundation for Parkinson and the Retardation and Red Syndrome, and the Fragile X foundation for Fragile X. The foundations provided access to their experts, who tested the team's molecule in the respective animal model of the disease, with positive results. Both the Red Foundation and the Michael Fox Foundation founded clinical studies after preclinical confirmation, which helped the team leverage external resources at a lower cost while still making progress. 

Anavex's Focus on Precision Medicine in Developing New Treatments 

Question: What is precision medicine and how does it relate to Anavex's approach to developing new treatments? 

Answer: Precision medicine is defined by identifying a biomarker that correlates with disease reduction or patient benefit, which Anavex uses to follow their drug. While the drug works for all patients regardless of genetic background, some patients respond even better, allowing for identification of patients who benefit most. Anavex's drug benefits the majority of patients with the wild type gene for the Sigma 1 receptor, making precision medicine an essential component of their approach to drug development. 

The future of the pharmaceutical industry in the field of Alzheimer's disease 

Question: Where do you see the future of the pharmaceutical industry, especially in the field of Alzheimer's disease? 

Answer: The future of the pharmaceutical industry in the field of Alzheimer's disease is moving towards whole genomic analysis, similar to the approach taken in the oncology space. Anavex includes whole genomics in all its clinical trials to understand the entire gene of a patient, both in the active and placebo arms. 

Presentation 

Advancing Precision Medicine for Neurological Disorders: An Overview of Anavex's Late-stage Pipeline and Future Strategies 

• Anavex Life Sciences is a New York-based company that focuses on discovering and developing late-stage drugs for neurological disorders, rare diseases, and other serious conditions. 

• The company's precision medicine identifies biomarkers that are hard to find in CNS and works with the body's defense mechanism by activating a protein called Sigma 1 receptor to restore cellular balance and homeostasis. 

• ANAVEX®2-73 is a small molecule drug that activates the body's defense mechanism from the outside to provide therapeutic benefits for patients with Parkinson's disease, Rett syndrome, and other neurological disorders. 

• Clinical studies of ANAVEX®2-73 have demonstrated successful outcomes, particularly in patients with higher levels of Sigma one expression. 

• Anavex Life Sciences has completed a Phase 3 study in Ultimate Disease and is planning to test ANAVEX®3-71 in a clinical study for Alzheimer's disease and schizophrenia. 

• The company has successfully completed a Phase 2 study in Parkinson's dementia and is planning to conduct a Phase 3 study and a pet study, supported by Michael Fox Foundation, for Parkinson's dementia. 

• Anavex is also planning to read out a phase 3 study called "Excellent Study" in pediatric patients with Rett Syndrome in the next few months. 

• The company is also looking into collaborating with companies around the world for areas where it would be at a disadvantage to market the drug itself, for example, in Asia. 

Q&A session 

The Benefits of Targeting Upstream Receptors in Complex Diseases 

Question: Can you explain how the technology proprietary platform differs from traditional drug development strategies and how it may offer advantages in terms of efficiency and safety? 

Answer: The technology proprietary platform approach targets the Sigma one receptor, which is upstream in the body's pathways, unlike traditional drugs that target downstream receptors. This allows the body to decide what to block or activate, which can be more appropriate for complex diseases. This approach has the advantage of allowing the body to respond to the pathology, rather than limiting the treatment to a selected downstream target. This approach has shown success in improving motor scores in Parkinson's disease and reducing dementia in dementia patients. The analogy to this approach can be seen in oncology, where the most successful drugs are those that activate the body's immune system to help fight cancer. Overall, the technology platform approach helps the body to help itself in the CNS, offering potential advantages in terms of efficiency and safety. 

The Development and Clinical Validation of Sigma 1 Receptor Activation 

Question: Can you provide some background on the development of this technology? 

Answer: Yes, this technology was developed in the early days of the company foundation and has since matured. The concept has already been approved. The Sigma 1 receptor has been a field of interest, and new publications are confirming the benefits of Sigma one activations. This mechanism is a body-owned defense mechanism that affects many pathways, but it has shown to reduce neurodegeneration with clinically validated endpoints such as cognition and function, improvement of patients from baseline, and restoration of impairments in neurodevelopmental disorders such as Red Syndrome and Fragile X. 

The Importance of Collaborations and Partnerships in Advancing Research 

Question: Can you explain how your partnerships with institutions and foundations work and how you structure these collaborations to make them more efficient? 

Answer: We have been fortunate enough to find scientific rationale and support from institutions and foundations such as the Michael J. Fox Foundation for Parkinson's disease, the Red Syndrome Foundation, and the Fragile X Foundation. These organizations accepted our drug and tested it in their animal models, which led to successful clinical trials. We build trust by explaining the scientific rationale behind our compound and ultimately, it is a question of trust and conviction that our compound can deliver. These partnerships have been successful due to the organizations' belief in our compound and our ability to deliver positive results. 

ANAVEX®2-73 Clinical Trial Results and its Potential Impact on Alzheimer's Patients 

Question: What do the promising results of ANAVEX®2-73 mean for potential Alzheimer's disease patients, and what are the criteria for selecting patients for the clinical trial? 

Answer: The clinical trials have shown that patients with significant Alzheimer's disease who received ANAVEX®2-73 actually reversed their cognitive impairment and improved their activities of daily living, rather than just slowing the decline. This is an exciting result that shows the potential for patients to change the course of their disease pathology. To be enrolled in the trial, patients must have confirmed Alzheimer's pathology, Parkinson's pathology, Parkinson's dementia, or a genetic mutation for Red Syndrome. The confirmation of their disease is necessary before starting the trial. 

ANAVEX®2-73's Potential Market Size and Commercialization Plans 

Question: Based on the patient criteria, what is the potential market size for ANAVEX®2-73, and what are the company's plans to address this market? 

Answer: The current market size for ANAVEX®2-73 is around 67 million patients within the specific indication group, but this number could expand if the drug is used to address other indications. The company recognizes that this is a very large number, and they are actively working on plans to address this market. 

Question: What is Anavex Life Sciences' plan for commercialization and accessing patients globally? 

Answer: Anavex Life Sciences plans to market the rare disease indications on their own, but for larger indications, they will partner with larger pharmaceutical companies, including in the Asian region. They aim to retain as much upside as possible for shareholders but recognize that partnering may be necessary for certain regions they cannot cover themselves. Different scenarios and indications will also be considered. 

ANAVEX®2-73's Differentiation from Other Parkinson's Disease Treatments 

Question: How do you see Anavex’s treatment for Parkinson's disease different from other treatments currently available? 

Answer: There are not many drugs approved for Parkinson's dementia and there is a large unmet need. Current treatments for Parkinson's disease are only symptomatic and not disease-modifying. The speaker's drug, which is taken orally once daily, has demonstrated disease modification without the need for PET scans or injections. The recent approval of an antibody called Lukanov, which targets a new degeneration in the pathology, has been positive for the speaker's drug as it could be very synergistic. The speaker thinks their drug could be complementary to other treatments rather than a first-line treatment. 

Developing Biomarkers for ANAVEX®2-73 and Clinical Trials for Rett Syndrome 

Question: What is the plan for the development of specific biomarkers for ANAVEX®2-73? 

Answer: The plan for ANAVEX®2-73's specific biomarkers is to monitor the biomarker response based on Sigma one levels. The drug has shown clear evidence of a biomarker response and all patients benefit, but some patients with a wild type Sigma 1 gene respond slightly better. The company is currently observing how this would affect their market strategy and deciding between giving the drug to all patients or separating pricing for those who respond better. 

Question: Do you expect to see more benefit for babies with Rett syndrome in the clinical trial? 

Answer: The clinical trial for Rett syndrome is being conducted in patients aged five and older as there is too much variability in the behavior of younger patients. However, there is a likelihood that younger patients may have better results with earlier treatment. The trial will select patients with a confirmed mutation of the Mac two gene, which is the cause of the disease. 

Comparison of ANAVEX®2-73 and ANAVEX®3-71 mechanisms of action 

Question: What is the difference in the mechanism of action between ANAVEX®2-73 and ANAVEX®3-71? 

Answer: While the mechanisms of action are relatively similar, ANAVEX®2-73 and ANAVEX®3-71 are completely different drugs. ANAVEX®3-71 targets M1 agonist receptors in addition to Sigma one, while ANAVEX®2-73 targets several muscarinic receptors, but not M1 as strongly. Both drugs have different Sigma one activity or affinity and shades of variation. The clinical data for ANAVEX®3-71 in Alzheimer's or Parkinson's disease is not available yet, but preclinically the two drugs are very similar.  

Partnering plan in Asia  

Question: What is the ideal partner for ANAVEX® in Asia, especially in China? 

Answer: ANAVEX® is looking for a partner in Asia, particularly in China, who has experience in marketing novel drugs and therapeutics and has the resources to reach a large number of patients in the Asian market. They want a partner with the ability to handle indications as large as Ultimate pockets.