Tailoring Antibodies to Suit Emerging Diseases with Ichor Biologics
Updated: Apr 10, 2021
Welcome to Molecular Ideas and thank you for sharing your time with us. Today, we explore how Ichor Biologics is leveraging its next-generation platform to harness and improve on nature’s supreme defensive weapon: antibodies.
With new vaccines beginning to roll out across the world, it is becoming easier to view COVID-19 as a once-in-a-generation plague that will soon leave our daily dialogue. Unfortunately, pathogens are continuously waging war on humanity. Established pathogens like tuberculosis, HIV and influenza continue to develop drug resistance are becoming progressively more difficult to treat. In addition, emerging pathogens like COVID-19 expose how (un)prepared we are to manage novel emerging infectious diseases.
Three critical factors exacerbate this threat of infectious diseases:
a) A lack of technological infrastructure to quickly tailor therapeutics to novel infectious diseases as they emerge.
b) Pathogens are continuously evolving to more efficiently infect humans and resist established treatments.
c) The antimicrobials market is stifled by low returns to other therapeutic categories due to insufficient pricing incentives and mismatched market expectations.
Simply put, we need new therapeutics to treat infectious diseases as they emerge to avoid potential epidemics and bioterrorism treats. So, how do we overcome the obstacles of continuous pathogen evolution, the lack of technological development and poor market incentives?
As the name of the company implies, Ichor Biologics is leveraging a novel antibody development platform to identify, design, and refine one of our body’s most potent weapons against infectious disease: monoclonal antibodies. Antibodies are large proteins produced by the B ‘memory’ cells of the immune system. Unlike other broad-based chemical weapons of the immune system, antibodies are unique for their ability to bind a specific antigen – material that is perceived by the body as foreign and dangerous – with startling affinity and efficiency.
“Throughout history, infectious diseases have repeatedly decimated human populations; however, humans are highly adaptable and made to survive. In the case of fending off infectious diseases, the breadth of diversity amongst immune systems enable humans as a population to survive any pandemic disease.” says Ray. “We’re leveraging that diversity to make better therapeutics as the cornerstone of our platform.”
Ichor Biologics’ platform is based on a unique three-stage approach to capitalize on our innate immunological diversity – and improve on nature’s design while saving time and money in the process.
The process of antibody discovery and development begins by identifying patients with a broad range of symptom severity. While individuals may face the same strain of a cold, flu, or COVID-19, many of us present varying degrees of symptom severity. Some are asymptomatic; others need to be hospitalized. What makes those differences in symptom severity possible is how our well our immune system produces antibodies that accurately target the specific virus’ antigens. After taking blood samples from these patients, the Ichor Biologics team leverages cutting-edge, proprietary assays to identify which antibodies produce highly effective sterilizing immune responses.
However, simply identifying the ideal human antibodies doesn’t explain how to recreate them for further testing and eventual therapeutic use. In biology, form follows function. In this respect, antibodies bind to antigens to mediate or modulate their function.
The second phase of Ichor’s platform involves a process called ‘baiting’, which helps them identify the optimal antibodies to move forward. Ichor has developed an extremely efficient system to display antigens in their native state, which more faithfully represents the overall structure of the antigen. By understanding the true structure and shape of the antigen, the Ichor Biologics team can ‘fish out’ the antibodies that bind most tightly to the antigen – increasing the odds of vastly improving therapeutic efficacy in later trials.
Using this platform, we now know what our target antigen and our antibody would look like. The third phase of Ichor’s platform allows them to save and money while improving clinical outcomes by knowing both sides of the puzzle: they refine their target antibodies in silico.
The team has developed proprietary AI and machine learning tools to refine the fit of antibodies to viral antigens. This process normally demands extensive trial-and-error in pre-clinical and clinical development. This testing method can be incredibly time-consuming and costly, which keeps many new therapeutics from the market. By streamlining this process, Ichor Biologics can greatly reduce the times and costs normally associated with drug development.
This efficiency has profound implications for saving lives and how we make these critical therapeutics accessible.
There is a broad spectrum of pathogens emerging from nature in the developing and developed worlds that have no treatments and no vaccines. Twelve months ago, COVID-19 was one of them. Ichor Biologics’ mission is to ensure that we can defend against these emerging and re-emerging (i.e. drug-resistant) threats.
Ray and I discussed how his team is validating their platform in work against hantavirus – a dangerous and emerging global threat.
“Hantavirus is an emerging infectious disease that infect approximately 100,000 to 200,000 people per year. Some strains have 35%-40% mortality, with no specific treatment or vaccine. For these reasons, Hantaviruses are a real concern for the DoD, and CDC due to its devastating potential for a pandemic and use as a bioterrorism agent.”
To date, the NIH has tested and demonstrated that Ichor’s antibody-based therapeutics protect 100% of animals from an otherwise lethal dose of hantavirus (as seen in this Science Translational Medicine journal article by Garrido et Al). For this reason, Ichor’s hantavirus therapeutic represents a breakthrough for reducing the risk posed by these viruses as emerging pathogens and potential bioterrorism agents.
Beyond hantaviruses, Ichor has used its platform to help address the current COVID-19 pandemic. Early on, they gathered samples from infected individuals to understand what governs COVID-19 disease severity with the hope of making better therapeutics. Along the way, this work let to key breakthroughs that helped Ray and his team to develop diagnostic assays that predict whether a COVID-19 positive-patient will develop severe symptoms.
“If you can identify patients at risk for developing severe symptoms early on in the disease, we can intervene at earlier timepoints with more aggressive therapies, like monoclonal antibodies, and hopefully save lives.”
Hantaviruses and COVID-19 are only two of the thousands of emerging diseases that fall ‘below the radar’ of established therapeutics companies. Ray and his team are seeking to turn this market failure into a major opportunity.
Developing new therapeutics typically carries a price tag of ten years and $2.35 billion. When coupled with the historically low payouts in this sector, most large pharma companies have all but stopped any development in the infectious disease space. However, Ichor’s platform has enabled Ray and his team to cut these costs by orders of magnitude, while increasing their likelihood of regulatory success. Since the FDA approval rate for antibody-based therapeutics is about two times higher than traditional small-molecule drugs, even minor cost and time savings provide an outsized payout.
“That’s part of the problem.” says Ray. “The market incentives just aren’t there when you’re using more conventional technology for therapeutic development, so while there is a clear and present need for therapeutics in this space, not a lot of development is happening.”
“A big part of the problem is that people still want something as cheap as a [generic] antibiotic, since most economies in the developing world can’t support the costs of something more expensive like antibody-based therapeutics. However, what we have to take into account is that the developing world pays a big price when we ignore these disease as they inevitably infect our population, especially in a world with continuously globalizing economies. I think COVID-19 has been a perfect illustration for this effect and hopefully acts as a wakeup call to start incentivizing therapeutic development in this space."
Despite the current market incentives Ray and his team aren’t going to stop from continuing to tackle this problem. Unlike most early-stage companies, Ichor Biologics has already established efficient international operations in Chile to help facilitate cost-effective validation of their platform with the help of the team’s co-founder.
“Without VC backing [as a new startup] in New York City, it’s hard to get much space and you only get a certain runway for therapeutic development. We had to ask ourselves, ‘How do we build something with strong foundations that we can nurture into a viable company?’”
They’ve nurtured it well. Ichor Biologics is moving full-speed ahead towards clinical trials with their hantavirus antibody program. Of course, that’s just the beginning. A platform that can accurately isolate, analyze and improve on antibodies in silico will be not only be critical to preventing the next pandemic – there is potential for application in other therapeutic categories like oncology. A combination of speed, versality, and efficiency cannot be understated.
It almost sounds like science fiction; to the Ichor Biologics team, it’s just science.
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