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Sandra Coufal, Toragen, discusses her team's research targeting precancerous cervical cells, backed by a Gates Foundation grant and world-class advisors.

Inside the Expert Network Guiding TGN-S15 to Market

Sandra Coufal, MD, CEO, Toragen, outlines the scientific foundation and clinical ambitions behind TGN-S15 and her team's HPV-focused research, highlighting the exceptional expertise guiding their work and the significant unmet medical need they are working to address.

Central to the effort is Aldo Venuti, chairman of the scientific advisory board and a leading global authority on the HPV E5 protein. His institution, the Regina Elena Institute in Rome, serves as a sub-awardee on a Gates Foundation grant and provides crucial access to a rare precancerous cervical cell line originally licensed from the University of Cambridge.

This cell line is pivotal because it could allow the team to test their drug candidate against abnormal pap smear diagnoses. As Dr. Coufal explains, "If you could successfully treat abnormal Pap smears, over 99% of which are from HPV infection altering the cells, then you wouldn't have to have partial cervical resections." Such resections, when extensive, can lead to an incompetent cervix and loss of the ability to carry a pregnancy.

HPV is the most frequently transmitted sexual infection, affecting approximately 85% of sexually active people, with 10% unable to clear the virus on their own and no routine blood test yet exists to identify who those individuals are.

Rounding out the advisory team are Dr. Ezra Cohen, lead investigator on Keytruda trials in HPV-positive head and neck cancer; Dr. Penelope Duerksen-Hughes, an expert in HPV E5 and E7 proteins; and Dr. Bill DeGrado of UCSF, whose chemistry expertise continues to advance the program.

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Sandra Coufal, Toragen, shares promising Phase I results showing dramatic HPV DNA reductions and tumor shrinkage, with Phase II set to confirm efficacy and safety.

TGN-S11 and Early Indicators of Drug Activity

Sandra Coufal, MD, CEO, Toragen, discusses the methods used to measure drug activity in phase I clinical trial patients and what the encouraging early results mean for the study's next stage.

Dr. Coufal explains that the research team used two approaches to track treatment response. The first was a monthly blood test measuring circulating tumor HPV DNA numbers, a tool oncologists rely on to gauge whether a patient's therapy is working. "It actually decreases and precedes a decrease in size of tumors on CAT scan," Dr. Coufal notes, highlighting its value as an early indicator of what is happening in the body. The team observed dramatic reductions in HPV DNA levels among patients, signaling meaningful drug activity.

The second measurement approach was standard-of-care CAT scans conducted every six to eight weeks, aligned with known tumor cell doubling times. Results were similarly promising, with some tumors shrinking and others remaining stable.

Looking ahead to phase II, the team aims to enroll enough patients to reach statistically significant conclusions about partial and complete response rates. "If we had had more patients like we will have in phase II, then we get into being able to determine partial response or complete response, really more efficacy parameters," Dr. Coufal said.

Safety remains a priority as researchers work to identify the highest tolerable dose for patients. Dr. Coufal expressed confidence in the drug's profile, noting that the removal of the non-preferred enantiomer makes tolerability a lesser concern than it might otherwise be.

Sandra Coufal, Toragen, discusses advancing TGNS15 with strong IP, liquid formulation, and an accelerated FDA pathway, potentially saving millions on IND-enabling studies.

 How Toragen Is Fast-Tracking TGN-S15 to IND

Sandra Coufal, MD, CEO of Toragen, discusses the strategic approach to drug development, intellectual property, and regulatory advancement for the company’s lead compound, TGNS15.

Dr. Coufal explains why Toragen chose to advance TGNS15 over TGNS11. Since TGNS11 is a racemic compound tied to a generic, it offers limited IP protection. TGNS15, however, was an undifferentiated enantiomer before Toragen began its work, giving the company a stronger patent position. As Dr. Coufal notes, "Since it was an undifferentiated or a non-differentiated enantiomer prior to Toragen working on it, we actually have patents that are composition of matter patents, not just method of use patents." With those patents filed and method of use patents already granted, TGNS15 is the clear path forward.

Dr. Coufal also highlights a key formulation decision that the drug is available in liquid form, specifically designed to serve patients who cannot swallow pills. This method was developed for patients with head and neck cancers who have undergone disfiguring resections. "We wanted to be certain to have a liquid form available," she explains, adding that patients in this population "may have special tubes that they eat from."

On the chemistry, manufacturing, and controls front, Dr. Coufal shares that Toragen has successfully identified and crystallized its preferred salt form. The company is now focused on scaling up production to good manufacturing practice standards for human use.

Perhaps most significantly, Dr. Coufal explains that because TGNS15 derives from a compound with decades of human safety data, Toragen anticipates the FDA will require only a fraction of the standard investigational new drug-enabling studies that are typically required, which could save the company millions of dollars and considerable time on its path toward Phase II trials across multiple HPV-positive cancer indications.

Sandra Coufal, MD, Toragen, discusses advancing TGNS15 with strong IP, liquid formulation, and an accelerated FDA pathway, potentially saving millions on IND-enabling studies.

How Toragen Is Fast-Tracking TGN-S15 to IND

Sandra Coufal, Toragen, discusses how TGN-S15's preferred enantiomer showed no neurotoxicity and reduced tumor growth, supporting development of a safer, cheaper oral cancer drug.

From Bench to Pill Enantiomer Science and Oral Delivery

, Sandra Coufal, MD, CEO, Toragen, walks through the preclinical research that validated her team's preferred enantiomer compound for TGN-S11, Toragen’s small molecule inhibitor of the E5 oncogene protein, in patients with cancers associated with HPV.

Dr. Coufal describes two key rodent studies that shaped the direction of TGN-S11’s development program. The first was a neurotoxicity assessment, in which the non-preferred enantiomer triggered seizures in half of the test animals, while the preferred enantiomer showed no such effect. The second was a tumor model study using HPV-positive cancer cells, for which animals were treated for 69 days across three drug variants. The preferred enantiomer outperformed both the racemic compound and the non-preferred enantiomer in reducing tumor growth. As Dr. Coufal explains, "We were able to confirm the efficacy and also confirm the absence of neurotoxicity in the preferred enantiomer, and that's what gave us confidence to go forward."

From there, Dr. Coufal discusses the intellectual property strategy her team has pursued, focusing on patenting GRAS-designated salt forms of the preferred enantiomer. One salt form stood out for its pharmacokinetic profile, specifically a blunted peak drug concentration after ingestion. "That high Cmax in your bloodstream after taking a small molecule is what's really most associated with toxicity," Dr. Coufal notes.

Sandra Coufal, MD, Toragen, discusses how TGN-S15's preferred enantiomer showed no neurotoxicity and reduced tumor growth, supporting development of the oral cancer drug.

From Bench to Pill: Enantiomer Science and Oral Delivery

With news that the US Department of Commerce has 

initiated a national security-driven investigation into the import of pharmaceuticals

 and pharmaceutical ingredients, including finished drug products, active pharmaceutical ingredients (APIs), and their derivatives, it appears all but imminent that tariffs will be levied against these items in the near future. 

In fact, Commerce Secretary Howard Lutnick said in an 

 on Monday that "semiconductors and pharmaceuticals will have a tariff model in order to encourage them to reshore to be built in America," noting that the tariffs would be implemented within the "next month or two." 

Pharmaceuticals have so far been spared from the Trump Administration's reciprocal tariffs that were first announced on April 2, 2025. Since then, the Administration has placed a 90-day pause on most of those tariffs as negotiations take place. Still, the pharmaceutical industry is likely to see tariffs of 25% or more levied on drug imports, according to 

That move would be significant for drugmakers, given that a majority of APIs used in the US market are produced and imported from abroad from countries including China, India, and Ireland, among others. 

Seeing what's on the horizon, major drug makers including Johnson & Johnson, Eli Lilly, Merck, and Novartis have announced 

 into expanding their US-based manufacturing to fulfill the needs of the US market on its own turf. 

Reshoring efforts may be underway, but the threat of disruptions in the supply chain from impending tariffs seems to be driving a surge of exports from some of the world's biggest suppliers. According to a 

report from Ireland's Central Statistics Office

, pharmaceutical exports to the US increased nearly 280% in February 2025 versus the same month last year, suggesting that the US industry may be trying to stockpile pharmaceuticals in preparation for what lies ahead. 

 this week, Johnson & Johnson CEO Joaquin Duato said, "There's a reason why pharmaceutical tariffs [have historically been] zero. It's because tariffs can create disruptions in the supply chain, leading to shortages." He continued, saying, "if what you want is to build manufacturing capacity in the US, both in medtech and in pharmaceuticals, the most effective answer is not tariffs, but tax policy."

Johnson & Johnson estimated its potential tariff impact at around $400 million in 2025, primarily driven by China's retaliatory 125% import tax on US goods that would impact the company's medtech products that are shipped to China. 

Still, Duato doubled down on the company's capital investment in reshoring manufacturing, saying that the 

 to build out US production infrastructure would result in "essentially all [of] our advanced medicines that are used in the US [being] manufactured in the US."

While industry has begun to react to the cues put out by the Administration, many are still feeling a great deal of uncertainty about what lies ahead. During interviews with 

, from cautious optimism to concern about potential negative impacts on US investment in technologies developed abroad. 

"The biggest impact right now is on our ability to price components and lead time for things," said Peter Sarvey, head of sales for Automation NTH. "A lot of quotes, we would say, 'Here is a proposal for an automated system or automation line,' and that would be valid for 30, 60, 90 days or so. [Now] we have to make sure we keep a closer eye on things as the global dynamics of sourcing change. We do final assembly, and everything is designed and built here in the States for Automation NTH, but a lot of the components that we get, whether they be raw materials, aluminum, steel, or even the electronic components like sensors, cameras, or robots, are coming from overseas." 

Despite the uncertainty around the cost of goods and the downstream impact of those changes, some representatives are looking at the reshoring efforts as an opportunity for innovation.

"If we think about the impact that it potentially can have on the biologics industry, for example, it provides not only an opportunity but a strong incentive to on-shore manufacturing and potentially to actually do it in a way that, combined with automation, can create a kind of facility of the future," said Kerry Love, PhD, co-founder, CEO and president of Sunflower Therapeutics. "That's more of a distributed manufacturing concept or a micro facility like we're seeing revolutionize the electric vehicle space or new textiles or food production. So I think it's just time that we think about how this could be a driver for us to do something similar for protein and biologics production."

Articles

On April 14, 2025, the Trump Administration launched a national security-driven investigation into pharmaceuticals, a move that will likely result in tariffs being placed on pharmaceutical drugs, ingredients, and other components that are imported from outside of the United States. 

Pharmaceutical Tariffs Are Imminent: How Industry is Bracing for Impact

The pharmaceutical industry is at a pivotal moment, where advancements in manufacturing technology are set to redefine drug development and production. But the reality is that the move towards “pharma 4.0” requires a major shift, both ideologically and technologically, to adapt current processes to a framework that will automate much of today’s manufacturing. According to data collected as part of CRB’s Horizon Life Sciences report, 31% of industry players pointed to automation and digital transformation as key priorities for capital investment projects presently or in the near future. In a presentation at 

, Peter Walters, fellow, advanced therapies at CRB, discussed additional results from the report that shed light on priorities in both the lab and on the production floor, including AI, 

The Shift Toward Continuous Manufacturing

One of the major themes driving innovation is the shift from traditional batch processing to 

 and the increasing integration of digital technologies. This transformation is driven by the need for greater efficiency, cost reduction, and improved product quality.

Continuous manufacturing not only accelerates production but also allows for real-time quality control, reducing waste and ensuring more consistent product quality. According to the survey data, more than 75% of respondents are currently using or plan to implement continuous technologies within the next 5 years, including in cell seed/expansion, filtration, solution prep, and chemical/enzymatic reaction, among others.

“When we think about continuous manufacturing, where you’re really getting that quality product is when you can achieve a robust process that's running at an equilibrium; you've got very good control over that whole state,” Walters said during the presentation. “Your protein is coming out of the bioreactor much faster, so instead of a traditional batch where the protein is sitting in the bioreactor for 14 to 20 days, here it's coming out daily, so it's not sitting in all that byproduct...before it gets processed. It's getting purified in real time, and you're getting a higher quality product [and] you're getting better control over that product stream.”

Beyond continuous manufacturing, companies are investing heavily in artificial intelligence (AI) and data analytics to enhance their production capabilities. These technologies enable predictive maintenance, process optimization, and enhanced supply chain management, ultimately leading to faster drug development cycles. One key area of development and steep adoption is in inline sensor technology for real-time batch release and analysis, with a reported 40% indicating they use this now and an additional 38% planning to implement it in the next five years, according to the survey data.

About 85% of respondents indicated they were at some stage of planning or execution of the integration of AI in process data analysis in cGMP manufacturing, though there is still a great deal of caution around AI implementation in areas highly scrutinized by regulatory bodies, such as batch records.

“I know for some people the idea of AI in a cGMP-regulated setting could be a little unnerving, but it doesn't mean that we're handing over the sole finish to our robot overlords; it's a lot more like mechanical systems that have AIs on board to moderate themselves and look for mechanical issues in advance of them happening,” Walters explained. “I think where we also are seeing it is where you've got manufacturing steps that have to have very complex decision trees; you're still having a person make those decisions, but you're having AI models that can support that decision-making.”

Another crucial topic was the industry's responsibility to adopt sustainable manufacturing practices. With rising global concerns about environmental impact, pharmaceutical companies are exploring ways to minimize waste, reduce water consumption, and lower carbon emissions. But how do those efforts fit in with the move towards continuous manufacturing?

“The whole idea about continuous biomanufacturing, ie., higher productivity and lower cost of goods, is a facility that's running constantly. Because it's continuously running, your HVAC, your lighting, and your whole infrastructure are running the same amount, but you're creating more product, so it actually is getting a better return on your facility investment,” Walters said. According to CRB, an energy model demonstrated that a continuous facility operates 33% more efficiently than one that runs a more traditional batch process.

Among the respondents, energy and waste were top priorities when it came to sustainability, but Walters was keen to point out the differences between companies prioritizing being carbon neutral versus those with net-zero goals.

“Carbon neutral a lot of times means [that] maybe [you] aren't even making any slight changes in how you do processing; you can buy carbon offsets, which means you're spending money towards things like fighting deforestation or putting in counter measures that help try to pull out greenhouse gas; things that are maybe off-site. Whereas net zero is where you're really trying to reduce what you're doing on-site. You are trying to recycle your waste, you're eliminating how much water you're using, you're putting in photovoltaic and more renewable power situations, and you're moving to a more electrified facility.”

But to no surprise, none of this happens overnight, and converting existing facilities to operate more sustainably is a tall order, Walters confirmed. Challenges can vary by company size, facility type, products produced, and other factors. Notably, more than 50% of respondents said that they currently have conservation practices in place to recirculate lab air, and more than 75% have on-site water reclamation/recycling currently implemented, in design, or planned to be implemented in the next 5 years.

Despite the promising innovations, concerns about regulatory compliance and acceptance run rampant. The industry must navigate evolving guidelines from the FDA and the European Medicines Agency (EMA), ensuring that new technologies meet stringent quality and safety standards—a challenge that requires proactive engagement with regulators.

However, Walters was quick to point out that some of the fears about regulatory acceptance may in fact be imagined.

“FDA did an internal audit comparing traditional batch submissions to fully end-to-end continuous submissions, and they found that on average, application approval was 3 months faster for continuous and 4 months faster post-submission to market,” Walters said, challenging the general thought that regulators are a major hurdle in the switch from traditional batch to continuous manufacturing.

As the pharmaceutical manufacturing landscape continues to evolve, companies that embrace digital transformation, regulatory innovation, and sustainable practices will be best positioned for success. The presentation underscored the importance of collaboration between industry players, regulators, and technology providers to drive meaningful progress.

Recognizing that the biggest hurdle to adopting these new practices comes down to investment—not just monetary but time—Walters pointed out that startups are in a unique position to help push this technology forward, as they aren’t faced with the same hurdles of converting legacy sites and other large infrastructure burdens that larger, more established manufacturers face.

With significant change on the horizon, it’s critical that pharmaceutical manufacturers continue to adopt new technology and identify opportunities for innovation and efficiency in their processes.

The move towards “pharma 4.0” requires a major shift, both ideologically and technologically, to adapt current processes to a framework that will automate much of today’s manufacturing.