By bringing the efficiency and affordability of vaccines to chronic diseases such as migraines, U.S. company Vaxxinity aims to open a new frontier for vaccines in an effort to reach all patient populations, regardless of location or income.\n\n\n\nMigraine causes severe headaches that are characterized by throbbing pain and associated symptoms such as sensitivity to light, sound and smell; nausea; vomiting; and visual disturbances called auras. \nAn estimated 10% of individuals worldwide suffer from migraines, which occur most frequently in adults between the ages of 20 and 50 and are three times more common in females than in males. \n\n\n\nDespite affecting more than 1 billion people and being on the World Health Organization’s 10 most disabling medical illnesses, migraines have been overlooked -- similarly to other diseases that primarily affect women -- for several reasons, including gender biases in research and diagnosis.\n\n\n\nTreatment of acute migraines typically involves normal or anti-inflammatory painkillers and triptans, which target serotonin pathways. However, these nonspecific oral medications are discontinued by 80% of migraine sufferers after 12 months. \nNewer, targeted classes of migraine therapeutics that can abort or prevent migraine symptoms include gepants and monoclonal antibodies (mAbs). These drugs block calcitonin gene-related peptide (CGRP), a neurotransmitter released by sensory nerves that is involved in the migraine pathway. Despite providing relief for migraine sufferers, CGRP inhibitors are not easily accessible. \n\n\n\nmAbs are a powerful tool in modern medicine, and have been used to target a wide range of infectious and chronic diseases. They are currently dominating the drug development landscape, with a fifth of U.S. Food and Drug Administration (FDA) new drug approvals each year going to these biologics. However, mAbs are difficult to manufacture and administer, and carry a hefty price tag that has made them globally inaccessible: 80% of mAbs are only available in the U.S., Europe and Canada, which represent a small fraction of the global population.\n\n\n\nTo improve accessibility, the Texas- and Florida-based biotech Vaxxinity aims to democratize medicine by developing affordable vaccines for chronic conditions such as migraines, Alzheimer’s and Parkinson’s -- to name a few. By combining the power of mAbs and the convenience and affordability of vaccines, Vaxxinity’s synthetic peptide platform has the potential to deliver highly effective medicine for all. \n\n\n\nWe talked to CEO Mei Mei Hu about Vaxxinity’s mission to “conservatively” disrupt medicine by going after validated targets with a validated and de-risked vaccine platform -- instead of coming up with brand new technology, manufacturing and mechanisms of action -- and how their migraine candidate (currently in a phase 1 trial) can positively impact the quality of life of patients with migraines. \n\n\n\nHow does Vaxxinity’s Vaxxine platform work?\n\n\n\n\nAt its very core, Vaxxinity’s synthetic peptide platform turns the body into its own antibody factory against self antigens of chronic diseases. The body’s immune system is very smart and usually doesn't like to attack itself to avoid developing autoimmune disease. But we figured out a way to overcome that and trigger a targeted immune response by presenting the self antigen as a threat. \n\n\n\n\nIf we imagine the sheep as the self antigen, which the body does not respond to, we can dress it up in just enough wolf's clothing that when the body first sees it, it sounds alarm bells. In this case, the wolf comes from our proprietary library of synthetic T helper cells that do not exist in nature. These T helper cells mimic highly promiscuous epitopes that are, for example, found on the measles virus or tetanus toxin. And so when the body sees this, it immediately responds and begins to produce antibodies against the “sheep” or self antigen.\n\n\n\nmAbs also enlist the body’s immune system to fight off disease. How does Vaxxinity’s approach to stimulating the immune system against chronic diseases differ from that of mAbs?\n\n\n\nmAbs are antibodies that are manufactured outside the body in giant bioreactors and then infused or injected back into a patient. Vaxxinity’s approach instead teaches your body to become that bioreactor and produce these antibodies on its own.\n\n\n\nIt's like the saying, “Give a man a fish, and you feed him for a day. Teach a man to fish, and you feed him for a lifetime.” So mAbs are like continually giving the body a fish, whereas the vaccine is teaching the body to fish. And because the body is producing the antibodies itself, there's a longer durability associated with the treatment. Moreover, vaccines can last longer than mAbs, so you would only get dosed every quarter or every six months or even a year. \n\n\n\nMore importantly, the cost of the medicine is significantly reduced as producing mAbs is extremely expensive. Vaxxinity’s vaccines are synthetic peptide-based, so the chemical process needed to manufacture them can be scaled up much more easily and stably. Generally, our cost of goods is less than 1 percent that of mAbs.\n\n\n\nHow does Vaxxinity approach migraine treatment using the Vaxxine platform? \n\n\n\nThe UB-313 vaccine teaches your body to produce specific antibodies that target and suppress CGRP, which plays an important role in one of the migraine pathways. Research has shown that suppressing CGRP can significantly reduce the number of migraines people have. \n\n\n\nCGRP has several functions in the body, beyond its link to migraines. Could CGRP inhibitors or vaccines have negative side effects?\n\n\n\nWith all of Vaxxinity’s candidates, we first make sure that we're on target. So before we inject the first patient, we test for any off-target impacts to make sure we have a very clean profile. But we also rely on the research before us to show the safety. \n\n\n\nWe're a small company and we're trying to disrupt the way that medicine is delivered but we realize that we can't do everything. So we have a “Fast Follower” strategy, where we go after targets that have already been validated before. \n\n\n\nOne of the reasons we target CGRP is because it's already been tested. There is already data on millions of patients on CGRP-suppressing treatments, which have shown very good safety with the potential side effects being gastrointestinal issues. \n\n\n\nThere are already five CGRP inhibitor drugs on the market that work better and faster than conventional migraine drugs. What benefits can Vaxxinity’s vaccine offer over these inhibitors? \n\n\n\nOral pills and mAbs have shown a lot of promise and efficacy in reducing the number of migraines for people who respond to the CGRP pathway. However, they are late-line treatments because they are expensive. When migraine sufferers go to doctors, they are first put on the standard painkillers and triptans as they are accessible. If they don’t work well enough, patients can go on CGRP inhibitors.\n\n\n\nHowever, Vaxxinity’s vision is for patients to reclaim their lives by being the first choice for patients, payers and healthcare systems. The vaccine would not be as expensive as mAbs and can thus be accessible to patients upfront. And for the percentage of people where the vaccine doesn’t work, they can try something else on top of that.\n\n\n\nAnother benefit is durability. With migraine mAbs, patients have to inject themselves every month or go in for an intravenous infusion every quarter. This is challenging because some people don't like to inject themselves and not everyone can afford or even wants to go to the doctor at such a high frequency. So imagine instead going in for a vaccine once or twice a year. That's the main benefit for the patient: the convenience and longer lasting effectiveness makes the vaccine attractive.