The Demand for Antidotes in Pharma

There are many important markets in the pharmaceutical industry that address patient needs. But one market that may not be discussed as often as others is that of antidotes and the treatment of poisonings, toxicities, and more. In this exclusive Q&A with Pharmaceutical Executive, Christon Hill, chief innovation officer, SERB Pharmaceuticals, reveals the demand for antidotes, how the development and manufacture of antidotes differ from “traditional” pharmaceuticals, acquiring financial backing, antidotes the company is working on, and more.

Pharm Exec: Let’s talk about the demand for antidotes. What does that look like in 2023? Do you anticipate an increased demand?

Hill: Having been in this field for 20 years, we’ve seen how the COVID pandemic, the war in Ukraine, and (more recently) reports of terrorist activity in Western Europe have put health emergency preparedness and response higher on the agenda of governments, public health agencies, and militaries around the world. Those responsible for emergency planning are more conscientious about what they stockpile and what antidotes they may want to have on hand in a public health emergency.

To take one example—we sell potassium iodide products that prevent radioactive iodine from getting into the thyroid gland during a nuclear radiation emergency. Typically, these are stocked by those living near nuclear reactors as a precaution. We saw a huge increase in demand for these products from both governments and the public in reaction to the conflict in Ukraine—especially fighting around Chernobyl and the Zaporizhzhia nuclear power plant. In 2022, we doubled our manufacturing capability to meet these unexpected needs.

We’ve also seen greater interest in our development projects. Developing antidotes and securing the capabilities to respond quickly to new pathogens have taken on a renewed urgency for governments around the world. Everyone is trying to predict the next threat (which is difficult) and put things in place to be able to react to a range of threats. This will require close cooperation between public bodies, NGOs[non-governmental organizations], subject matter experts, and private companies with relevant experience and capabilities.

Pharm Exec: How do the development and manufacturing differ for antidotes vs. traditional bio/pharmaceuticals (if at all)?

Hill: Development pathways can be slightly different. For example, we could not ethically test an antidote in human efficacy trials. For example, take exposure to cyanide—we rely on FDA’s ‘animal rule’ and similar pathways in other jurisdictions.

There are very few major differences in manufacturing. Quality is important for any medicinal product, but even more for critical care and antidotes products. Continuity of supply and supply chain resilience is also of added importance when you are providing antidotes. All of our medical countermeasures for CBRN (chemical, biological radiological, and nuclear) [defense], including the active ingredients, are made in Europe, which is important to our government and military customers.

The key difference lies in the channels used once produced to ensure that the antidote is there when needed. Therefore, it is essential for us to work with our partners all along the supply chain to ensure the availability of our products.

Pharm Exec: How does acquiring financial backing differ for the antidotes market vs. traditional pharmaceuticals?

Hill: One difference is that promising research is more likely to attract public funding. In the US, this comes from groups such as the Biomedical Advanced Research and Development Authority (BARDA), which is tasked with preparing medical countermeasures for public health emergencies. In 2021, the European Commission launched an agency with a similar purpose called the European Health Emergency Preparedness and Response Authority (HERA).

Since 2017, SERB has been majority owned by Charterhouse Capital, one of the longest-established private equity firms operating in Europe. They believe in our mission and have supported our investment in acquiring and developing new antidotes.

Pharm Exec: SERB Pharmaceuticals has a large antidote portfolio. What got the company into this line of work?

Hill: SERB (Society for Biological Studies and Research) was founded in France in 1951 by two pharmacists. The company has always been focused on essential, niche treatments that meet high medical needs. That is at the core of SERB’s culture and growth strategy. Over the past 25 years, the company expanded its portfolio in emergency medicine and (especially) antidotes.

In the field of emergency medicine, each second counts; so, there are added challenges in consistently supplying these essential medicines and ensuring they are stocked close to where they may be needed. That’s why the company built a regulatory infrastructure and a network of distributors that would allow us to make its products available throughout the world. We want to be an essential partner for first responders, healthcare professionals, NGOs, and governments. Often, this means being flexible and adapting to the requests of customers who are dealing with or preparing for emergency situations.

In 2021, SERB acquired BTG’s specialty pharmaceuticals business, which was focused on antidotes sold primarily in the US. This has given the company a truly global footprint along with what we believe is the broadest antidote portfolio in the world.

Pharm Exec: Your company specifically works with polyclonal antibodies. How are your polyclonal antibodies made?

Hill: SERB is one of the few companies in the world manufacturing polyclonal antibodies at a commercial scale—and to rigorous quality standards—with a process robust enough to satisfy regulators in all territories. For more than 20 years, we’ve used this technology to produce two commercially-available products. More recently, we have begun to use this platform to develop novel biologic therapies against a wide range of toxins, drugs, and viruses for use around the world.

Our antibodies are produced by immunizing sheep at our facility in Australia with an antigen that the antibodies will be directed against. The antigen is specific to the toxin we are trying to develop an antidote for. The animal’s immune system responds to the antigen by producing a mixture of different antibodies, which are then collected from the animal’s blood. In our facility in Wales, the binding end of the fragmented antibody (Fab) is separated from the rest of the antibody, known as the Fc (fragment crystallizable) region, and purified. These are delivered to hospitals as lyophilized products.

Pharm Exec: You’re developing a ricin antidote. Where can people be exposed to ricin? Why did the company choose to focus on treating this type of poison?

Hill: Ricin is a highly potent toxin produced in the seeds of the castor oil plant (Ricinus communis) and can easily be extracted and weaponized by terrorist groups. There are no government-approved therapies for ricin exposure, which is why we chose to focus on it. We believe that our antidote based on polyclonal antibodies against different cultivars of ricin could offer an effective solution, as shown in the in-vitro neutralization studies we conducted in 2022 [that are] soon to be published.

In January 2023, German authorities foiled a plot to deploy cyanide and ricin in a potential terrorist attack. German police prevented another terrorist group from launching a ricin attack in 2018. In the last decade, there were several ricin attacks in Europe and the US. There were also at least five reported cases of students creating ricin on university campuses in the US at that time. There have been numerous reports of letters containing ricin being mailed to the White House, the US Congress, the Pentagon, and other city, state, and federal officials.

Pharm Exec: What other antidotes are you working on?

Hill: We have a pipeline of targets to address additional toxins, infectious diseases, biological agents, and drug toxicities. We take input from a broad range of perspectives to assess medical needs and technical feasibility. This includes external advice from a scientific advisory board made up of global experts in public health, toxicology, and defense.

When the COVID-19 pandemic struck, we began a project to develop a polyclonal antibody that might be appropriate for severe infections among those unable to be vaccinated or not responding to other treatments. Results of early animal studies were presented at the Infectious Disease Society of America conference last October and showed that hamsters treated with the antibodies had a positive clinical outcome across a range of measures. These were early animal findings, but it demonstrates the potential to use our polyclonal antibody platform to develop new treatments for infectious diseases.

SERB has also disclosed that we are developing an antidote for fungal pathogens. Last October, the World Health Organization issued its first “fungal priority pathogens list,” which systematically prioritized fungal pathogens and called attention to the public health importance and the relative lack of R&D attention. We’re evaluating the role polyclonal antibodies could play in treating fungal infections as [either] an alternative or alongside traditional anti-fungal therapies.

Pharm Exec: What’s the typical administration process for antidotes?

Hill: Our products are sold in a range of formulations and from a wide range of galenic formulations to more exotic formulations, such as prefilled syringes, buccal administration, nasal sprays, and IV administration kits. Elsewhere in our portfolio, we also have products classed as medical devices. Having this range of expertise helps us meet the needs of hospital clinicians as well as first responders and the military.

Pharm Exec: What do you foresee for antidotes in the coming years?

Hill: One of our goals is for this platform to serve as a rapid response capability for newly emerging or previously unidentified risks. By standardizing and validating our processes and leveraging in-house expertise, we’re getting closer to offering a “plug-and-play” approach to generating novel antibodies that can quickly be developed into novel life-saving therapeutics.

I think the COVID pandemic helped demonstrate how valuable the industry can be in countering new threats to public health, but antidotes are also a challenging area of medicine. The range of unmet needs includes known areas of disease and toxicity, but (ideally) you’re also preparing countermeasures for novel, unknown, or re-emerging threats. It requires a slightly different skill set to effectively develop and commercialize products in this space.