Calibr-Skaggs scientists are advancing innovative medicines to help the world prepare for the next pandemic and transform medical care in regions that lack access to essential health services.

Drug discovery for global health

By the middle of the 20th century, tuberculosis was almost a forgotten threat in the U.S., its low incidence serving as a testament to medical triumph. Even now, with recent upticks, the disease still causes relatively few deaths.

But the U.S. is an outlier.

Tuberculosis continues to ravage communities around the globe, claiming more than 1 million lives annually. And it’s only one of many illnesses that knows no borders.

Although science and medicine have advanced at an astounding rate in recent decades, international health disparities are widening, and access to lifesaving medicines remains inadequate. While cardiovascular conditions are the world’s primary causes of death, infectious diseases dominate underprivileged areas. Tuberculosis is still among the most prevalent infectious killers, and millions of people become infected with malaria each year—a number that’s growing as antimalarial resistance looms. What’s more, far too little is being done to prepare for the next pandemic—a prospect that threatens everyone.

At the root of the problem are longstanding disconnects between global medical needs and ways that new medicines are developed and brought to market. These gaps include a divide between academic institutions and the pharmaceutical industry, a lack of financial incentives to create drugs for use in disadvantaged regions, and limited funding for nonprofits that seek to address such problems head-on.

To tackle these challenges, Scripps Research and its drug discovery arm—the Calibr-Skaggs Institute for Innovative Medicines—have emerged as trailblazers in this domain, confronting worldwide health concerns that have been left unsolved. Under the leadership of Pete Schultz, the founder and CEO of Calibr-Skaggs as well as the President, CEO and L.S. “Sam” Skaggs Presidential Chair of Scripps Research, both entities have become pioneers in transforming access to critical treatment on an international scale. A key strength: Calibr-Skaggs’ holistic strategy seamlessly combines basic academic research with drug development. This allows groundbreaking scientific findings from Scripps Research’s foundational research labs to guide the creation of medicines tailored to solve vexing global health problems.

As a mission-driven institute, Calibr-Skaggs develops “dual-use” medicines that can be utilized in high-income countries where they generate profit, and in low-income countries where there’s little commercial opportunity. The institute is also creating medicines specifically for diseases that plague disadvantaged regions but receive little—if any—attention from industry, including neglected tropical illnesses such as schistosomiasis and Chagas disease.

Because the institute is a nonprofit, funding derived from licensing and royalties of these novel therapies is reinvested back into basic research, ensuring a continual wellspring of discoveries that can be put to work to improve human health.

And Calibr-Skaggs is undertaking problems that other organizations can’t—or won’t. This is largely due to the institute’s focus on exploring ideas with far-reaching impact, combined with its ability to translate early-stage research into clinical proof of concept.

“The idea is to chaperone high-risk, high-reward programs from early-stage discovery through phase 1 clinical trials that demonstrate potentially transformative concepts for new medicines in patients,” explains Travis Young, the vice president of biologics at Calibr-Skaggs. “We can de-risk a new drug—which pharmaceutical companies are eager to see—understand the drug’s potential and determine which populations need the drug most. Our motivation isn’t profit: it’s impact on human health.”

To truly grasp specific problems and craft solutions, institute scientists travel to and collaborate with other countries. This provides a comprehensive sense of regional health care needs, which can be incorporated into research. Armed with their deep foundational knowledge and predictive preclinical models, scientists at Calibr-Skaggs have a better idea of how people will respond to treatments that haven’t yet reached the clinic.

“At the 2023 Grand Challenges Annual Meeting in Senegal, there were discussions about building the capacity to produce RNA-based vaccines for viral infections that specifically affect this region,” recounts Arnab Chatterjee, the vice president of medicinal chemistry at Calibr-Skaggs, who leads several institute projects. “On the other hand, developing certain small molecule drugs isn’t always common—even in higher-income countries—so you have to make sure you’re creating potential therapies that are effective and affordable.”

ReFRAME-ing medicine

Among Calibr-Skaggs’ paramount contributions to global health is ReFRAME: a drug repurposing library that permits scientists to rapidly test thousands of drugs that have been used in humans and determine if the drugs could treat nonindicated conditions. The concept behind ReFRAME was to provide a faster and cheaper way to get new medicines to patients.

Funded by the Gates Foundation, the library is the largest resource of its kind. And it’s free to use—as long as scientists who use it share their findings with the research community.

ReFRAME drugs already have human safety data, so using the library is an efficient way to move quickly from concept to clinic—and it’s often significantly cheaper to repurpose a drug than to create a new one. Previously, ReFRAME helped to develop novel treatments for COVID-19, osteoarthritis, heart failure, macular degeneration, pulmonary fibrosis and inflammatory bowel disease.

Calibr-Skaggs is now using ReFRAME to screen possible combined compounds to treat H5N1—an influenza virus that’s widespread across wild birds and has started to infect various mammalian species, including humans.

Building on lessons from the COVID-19 pandemic, the institute aims to identify treatments that can both prevent and combat infections, offering critical solutions during potential outbreaks while vaccines are still in development.

Preventing and treating infectious diseases

A chief focus of Calibr-Skaggs scientists is creating long-acting preventative medicines and single-dose treatments—both chemical- and protein-based—for infectious diseases such as tuberculosis, malaria and HIV. Distinct from vaccines that activate the immune system against infections, these compounds remain in the bloodstream for a long period of time and directly inactivate pathogens.

“Anything that can shorten treatment duration is expected to be a huge game-changer,” notes Young. “You’ll see fewer infections as well as more complete treatment courses, and the increase in compliance will reduce transmission.”

For example, Calibr-Skaggs is developing molecules for tuberculosis that wouldn’t only combat drug-resistant variants but also shorten the standard treatment period.

Every year, around 10 million people contract tuberculosis worldwide, resulting in more than 1 million deaths, according to the World Health Organization (WHO). Mycobacterium tuberculosis—the bacterium that causes the disease—is an airborne pathogen, meaning transmission occurs from inhaling infectious particles. Four antibiotics taken for up to six months is typically the first line of treatment.

“People don’t always have access to the full supply of a drug, or they don’t take the entire course,” says Sean Joseph, the vice president of nonclinical development at Calibr-Skaggs, highlighting this is frequently the case with both tuberculosis and malaria. “When a drug makes someone feel better right away, they often stop using it.”

That’s why Calibr-Skaggs is working on a single-dose cure as well as medicines taken in combination, known as adjuvants—which supercharge immune system responses—to enhance existing influenza vaccines. And by collaborating with the Medicines for Malaria Venture, with support from the Gates Foundation, a long-acting anti-malarial compound has recently entered a phase 1 clinical trial in the U.K.

Malaria, a parasitic disease often contracted through mosquito bites, disproportionately affects Africa. According to the WHO’s most recent malaria report, in 2022, there were nearly 250 million cases and 608,000 fatalities across 85 countries. Children younger than five years accounted for the majority of deaths in the WHO African Region.

“We would administer our ‘chemical vaccine’ once during the rainy season in the Sahel (a biogeographical region in Africa) to protect individuals from malaria, and we would give it to uninfected people cohabitating with others who have malaria to prevent disease contraction,” explains Joseph.

The ability to develop chemicals that remain in someone’s system for several months after a single dose—akin to a “chemical vaccine”—is a sophisticated complement to conventional vaccines.

On the HIV front, Calibr-Skaggs discovered a long-acting injectable that could be used for prevention or in combination with other treatments based on regional needs. The institute is now partnered with Gilead Sciences, Inc. for the clinical development stage.

Because HIV is currently incurable, it’s vital that individuals who are infected adhere to a strict, lifelong treatment regimen that suppresses the virus from replicating.

Typically, patients take three antiretroviral medicines from at least two drug classes. Options may include a medication cocktail combined into a single, daily pill. Some patients are also candidates for long-acting injectables—but these often require administration at least every other month.

Calibr-Skaggs’ collaboration aims to create a globally available drug administered once every four or six months, drastically expanding the length of time between treatments.

Collaboration is key

A main reason for success is Calibr-Skaggs’ synergistic relationship with Scripps Research, allowing for shared data, knowledge and expertise.

“Our scientists know that combining innovation with interdisciplinary collaboration is key to addressing global health challenges,” remarks Chatterjee.

This includes working hand-in-hand with international organizations like the Medicines for Malaria Venture. On the industry side, pharmaceutical companies AbbVie Inc., Gilead and Novartis AG have partnered with Calibr-Skaggs to leverage its nonprofit model for antiviral research, either through licensing or direct research collaborations. Funding from the National Institutes of Health—which sponsored the Center for Antiviral Medicines & Pandemic Preparedness at Calibr-Skaggs and Scripps Research—and the Wellcome Trust have fostered drug creation for an array of viruses with pandemic potential as well as neglected tropical illnesses common in disadvantaged regions.

But according to Chatterjee, the bottom line is coming together to identify specific medical obstacles of populations around the globe. This partnership among scientists could break down barriers to access and encourage the development of safe, effective and affordable treatments—ultimately leading to medicines without borders.

---