University of Warwick research demonstrates how to engineer “cell factories” that last longer and produce more chemicals, without needing antibiotics or complex engineering methods, paving the way for sustainable biotech that lasts.

Synthetic biology aims to engineer living cells, often bacteria, to become chemical factories, pumping out chemicals important to health care, industry, and the environment. To achieve this, genetic circuits (synthetic DNA programs) are inserted into bacteria to harness the internal machinery to produce the chemicals.

However, the existing efforts to create these ‘living factories’ have struggled because keeping genetically engineered cells working as intended is challenging. Under the stress of producing chemicals, they often stop functioning, mutate or lose out in competition to faster-growing mutant cells in the population, limiting their useful productive lifespan.

In this paper, published in Nature Communications, researchers from the University of Warwick have used detailed computational simulations that mimic how bacteria grow, mutate, and compete in the lab, to produce a new solution to optimize cell factories. Dozens of genetic engineering strategies have been evaluated to theoretically find a way to keep cell factories stable and produce high quantities of products over many generations.

Dr. Alexander Darlington, Royal Academy of Engineering Research Fellow and Assistant Professor, School of Engineering, University of Warwick said, “Engineered cells have a limited lifespan because they are under stress and prone to genetic errors, which results in mutations which destroy function. These mutants tend to grow quicker and come to quickly dominate the cell factory.

“The computational modeling that we have conducted here compared a number of different genetic strategies—’gene circuit controllers’—and found the best ones before we even got to the lab. We are now looking to engineer these strategies into bacteria to enhance longevity, production, and their robustness to mutation.

“We applied ideas from control engineering to design something-like a genetic thermostat which turns things up when it gets too cool or down when too hot. We found that the best results came from combining two self-adjusting feedback systems: one sensitive to production and one sensitive to growth rate. Acting together, these negative feedback systems are predicted to increase the function of our engineered cells by threefold. It turns out that balance is the key: our systems are predicted to balance function with growth so that there is a small chance of takeover by mutant cells.”

The optimal strategy, using negative-feedback systems, works through inserting genes that act like sensors and monitor cell growth rates and cell output and then automatically adjusting gene activity to keep everything running smoothly. The slight drawback is a reduction in the production rate of each cell but thanks to the significantly longer lifespans, cumulative chemical production over time is much higher.

Dr. Darlington added, “After a gene circuit is inserted into a cell, making the chemical product uses its energy and resources, which slows the cell’s growth and favors mutations that will shut down the engineered gene circuit that is producing the protein. We have developed a sophisticated mathematical model which captures cell growth, protein production, mutation and selection and coupled this with optimization techniques to design multiple different genetic control strategies—now the exciting part is testing them in the lab.”

The proposed approaches would not need antibiotics (reducing the potential for antibiotic resistance) or complex engineering efforts (requiring more expensive rounds of experimental tinkering). The team believe their approach simplifies engineering efforts and could reduce product development times.

The proposed methods can be easily applied to different systems without the need for significant redesign, and can be incorporated alongside existing approaches, contributing towards the ultimate goal of synthetic biology applications that perform robustly and reliably in the long term.

To dramatically increase coral survival rates, scientists at the University of Hawaiʻi at Mānoa Hawaiʻi Institute of Marine Biology (HIMB) have developed innovative 3D-printed ceramic structures that provide crucial protection for baby corals. These new designs offer a low-cost and scalable solution to enhance reef recovery worldwide.

The discovery, published in Biological Conservation, addresses a critical challenge in reef restoration—the low settlement and survival rates of juvenile corals, which often die before adulthood due to predation, being overgrown by algae or being swept away by waves.

“We developed structures that help baby corals find safe homes in the reef,” said Josh Madin, principal investigator at HIMB’s Geometric Ecology Lab and co-author of the study. “Our new designs, with small spiral-shaped shelters called ‘helix recesses,’ give young corals the protection they need during this critical stage.”

Increased baby coral settlement

The study found that these sheltered spaces had about 80 times more baby corals settled on them compared to flat surfaces and helped them survive up to 50 times better over the course of a year. The idea was inspired by observing coral larvae in nature, which almost always chose small crevices to settle.

“We wondered if we could recreate these safe spaces in structures that could be easily added to reefs for restoration or built into coastal engineering projects,” said Jessica Reichert, lead author of the study and a postdoctoral researcher in HIMB’s Geometric Ecology Lab.

To test this, the team designed and deployed seven different 3D-printed reef modules at two sites in Kāneʻohe Bay. Over the next year, they tracked the settlement and survival of coral recruits, finding the helix recess design to be the most successful.

“We expected the helix recess design to help, but we were surprised by the scale of improvement,” said Reichert. “Seeing thousands of baby corals clustered in these tiny shelters, compared to almost none on flat surfaces, was remarkable.”

Simple to maintain

This method offers a significant complement to current restoration efforts that are often limited by the high cost and labor of rearing and outplanting coral fragments. The new structures are simple to produce, require no ongoing maintenance, and can be integrated into artificial reefs, seawalls, and other coastal infrastructure.

For Hawaiʻi, where coral reefs are vital for coastal protection, fisheries, and cultural heritage, the implications are particularly significant. “Developing and testing these designs in Hawaiʻi allows the UH to provide practical, locally driven solutions that help preserve the ecological, cultural, and community benefits reefs provide across the islands,” said Madin.

This research was conducted as part of the Reefense: Rapid Resilient Reefs for Coastal Defense (R3D) program. The project’s goal is to develop hybrid reef structures that act as living breakwaters to reduce coastal erosion. The helix recess design is intended to attract and shelter coral recruits within these larger structures, helping to create self-sustaining reef systems.

The agency estimates that about 86% of staff can remain in the event that funding stops, but new drug applications cannot be accepted.
The federal government is heading for a shutdown at midnight if no deal is reached between Republicans and Democrats on the hill. That means the situation at the FDA, which has already been plagued by approval slowdowns caused by mass layoffs, will be exacerbated.

But the FDA will not be affected as badly as some other agencies, since at least 86% of the agency’s staff will be able to continue operations, according to a guidance document on the impending shutdown. About 66% of those staffers are covered by user fees or other carryover funds.

Lawmakers on Capitol Hill in Washington have until midnight Tuesday to reach an agreement to fund the government, but both sides remain at an impasse, NPR reported Tuesday morning. At issue is a spending bill that Democrats have refused to back in an effort to force Republicans to negotiate on supporting federal healthcare subsidies that will expire by year end without both parties’ support. Leaders from both parties met with President Donald Trump at the White House Monday in hopes of securing a deal, but none was achieved.

That leaves the government hurtling towards a shutdown. Leerink Partners spoke to former Senator Richard Burr, who previously represented North Carolina as a Republican, and another unnamed senior counsel key opinion leader (KOL) for guidance on the shutdown. The KOLs advised that a shutdown is imminent with a deal highly unlikely. The shutdown could last as long as a month if there is no resolution within a week.

“A shutdown will not affect the funding of existing FDA reviews, though resultant noise may cause some delays,” Leerink wrote.

Within the Health and Human Services umbrella, research that depends on grants from the National Institutes of Health for medical research will be most impacted, the KOLs told Leerink. But the “anecdotal” slowdown in FDA action on approval applications will be “exacerbated modestly.”

Any activities that are funded via carryover user fees and anything covered by unlapsed funding will continue. That would include “certain activities” related to regulating drugs, since user fees cover these processes. The FDA can also continue reviewing requests to conduct clinical research and work on certain guidance documents. Leerink said the FDA does not typically use all of the user fees that are collected, so those can fund the agency for longer in the event of a shutdown.

But the FDA would not be able to accept new drug or biologic applications or complete any activities that would require the payment of a user fee, if the shutdown occurs. So any company that had planned an imminent new drug application would have to wait until the shutdown is over.

The unnamed KOL told Leerink that “since Trump took office, he has noticed a slowdown in FDA review processes, characterized by frequent breakdowns in communication between the FDA and applicants.”

Some companies have reported FDA delays, too. “He predicts that the noise from a shutdown may further delay reviews and approvals to some extent,” Leerink continued.

The FDA also noted in its guidance that the agency would not be able to work to curb compounded drugs, which has been a major issue over the past few years with the best-selling GLP-1 obesity drugs. This work could only resume if “necessary to assess or address imminent threats to the safety of human life,” according to the guidance.

The last government shutdown in Trump’s first term, lasted 35 days.

Pfizer CEO Albert Bourla directly credited the threat of tariffs with leading to the deal, in which the company will offer drugs on a soon-to-be-launched website called TrumpRx.
In a Tuesday morning press conference in the Oval Office, President Donald Trump, flanked by a coterie of cabinet officials, agency regulators and Pfizer CEO Albert Bourla, announced that the company has struck a deal with the federal government to offer some of its drugs at reduced prices.

The deal contains multiple parts. The first is that most of Pfizer’s primary care drugs, along with some drugs for specialty indications, will be available at an average discount of 50% on “TrumpRx,” a soon-to-be-launched website.

In return, Pfizer will receive a three-year grace period reprieve from the effects of potential pharmaceutical tariffs, as long as the company continues investing in U.S. manufacturing. Pfizer announced during the press conference that it will pump an additional $70 billion into its U.S. manufacturing footprint. Bourla directly credited the threat of tariffs with the company’s willingness to work with the administration.

“In our industry, we had two major overhangs that . . . create concerns for us in our ability to invest,” Bourla said. The first, he continued, is the uncertainty of tariffs, “because the president is absolutely right; tariffs are the most powerful tool to motivate behaviors, and they clearly motivated us.” The second, Bourla said, is what will happen with the framework of pricing in the U.S. “We are addressing both of them right now.”

While Pfizer said it is offering these prices to Medicaid recipients, it was not clear from the announcement how the company’s agreement—or any other similar agreement with other pharma companies—would align with private health insurance practices in the U.S. Trump noted the White House has been in talks with other Big Pharmas, specifically highlighting that “Eli Lilly has been fantastic.”

The third part of Pfizer’s agreement is parity, where the New York–based company will ensure U.S. patients receive prices similar to those of other similar, developed countries, a key plank in the president’s oft-repeated Most Favored Nations drug pricing scheme.

Medicare Director Chris Klomp spoke at length during the announcement, touting the arrangement.

“This is direct access for patients at Trump RX,” he said of the site, “available often at full MFN and always at lower prices than currently available. This is bypassing middlemen.”

“This is American ingenuity, outsmarting the system.”

Klomp walked away from the lectern to a poster board on the other side of the Oval Office to note price reductions on four of Pfizer’s drugs, including Eucrisa for atopic dermatitis (discounted at 80%), Duavee for post-menopausal osteoporosis (85%) and Xeljanz for rheumatoid arthritis (40%).

The S&P’s XBI biotech index has not moved significantly on the news, though the shares of individual pharma companies that have announced manufacturing pushes in the U.S. of the type that Pfizer said spared it from tariffs have gone up. Pfizer is up 7.5%, AstraZeneca 3.5%, Merck 5%, Eli Lilly 3.5% and Amgen is up 3%.

The centerpiece of the acquisition is petosemtamab, Merus’ bispecific antibody targeting EGFR and LGR5, which in May demonstrated best-in-class potential for head-and-neck cancer.
Genmab has won the race to buy cancer biotech Merus, putting down $8 billion to take over the Netherlands-based biotech and its oncology pipeline of bispecific antibodies.

Under the acquisition agreement, Genmab will purchase all of Merus’ common shares for $97 apiece, which represents a 41% premium to the biotech’s closing price on Friday. The companies expect to complete the transaction in the first quarter of 2026, pending regulatory clearances and the approval of at least 80% of Merus shareholders.

Reporting from Bloomberg News on Sunday revealed that several pharmas have been courting the cancer biotech in recent weeks, and that Genmab appeared to have been leading the pack. Genmab and Merus were in advanced talks, according to Bloomberg, which cited sources who requested anonymity and who cautioned that, at the time, a deal was not guaranteed.

BMO Capital Markets addressed the rumors in an investor note Monday morning, ahead of the official acquisition announcement. While the analysts conceded that the takeover talks come “as a little surprise” given how Merus’ pipeline has been performing, such a deal would nevertheless point to the “growing interest” in the biotech. Merus’ shares have shot up 63% year-to-date.

In a prepared statement on Monday alongside the acquisition announcement, Merus CEO Bill Lundberg called Genmab a “leader in antibody therapeutics,” adding that the Danish pharma “has the right vision and experience” to take its star asset petosemtamab forward.

Petosemtamab is a bispecific antibody designed to target the EGFR and LGR5 proteins, a mechanism that activates the immune system’s anti-cancer activity. In May, the biotech announced that petosemtamab aced a Phase II trial in head-and-neck squamous cell carcinoma, hitting a 79% overall survival rate at 12 months when used with Merck’s Keytruda. The regimen also elicited an overall response rate of 63% and a median progression-free survival rate of 9 months.

Reacting to the readout, William Blair analysts at the time said petosemtamab had a “best-in-disease profile” for the indication, unlocking a “potential blockbuster market opportunity” for Merus. Leerink analysts were similarly bullish on petosemtamab, noting that its combination with Keytruda could “become the standard of care” in this disease.

Genmab’s acquisition of Merus also reads positively for the wider biopharma industry, according to BMO on Monday. “We are encouraged by news of M&A discussions following lagging M&A activity over the last few years,” the analysts said, pointing particularly to Pfizer’s $4.9 billion Metsera takeover last week.

These deals, they added, “could start to spur broader M&A in the sector.”

The FDA in September issued two rejections for spinal muscular atrophy therapies—both linked to manufacturing problems—and granted approvals in Barth syndrome and for a subcutaneous version of Merck’s Keytruda that could be key to the blockbuster’s future earnings.

September was a busy month for the FDA, which issued a key approval for Merck’s Keytruda, one that should help the pharma shore up its sales as the blockbuster’s loss of exclusivity approaches. The regulator also approved Eli Lilly’s oral SERD Inluriyo for patients with certain types of breast cancer. Meanwhile, the rare disease space saw key approvals in Barth syndrome and acromegaly but suffered two rejections linked to manufacturing problems.

Read below for more.

Stealth’s Long Barth Syndrome Journey Ends in Approval

After more than a decade of research and regulatory discussions, Stealth BioTherapeutics on Sept. 19 finally secured FDA approval of its Barth syndrome therapy elamipretide, now to be marketed under the brand name Forzinity.

Barth syndrome is an ultra-rare, mitochondrial disease affecting around 150 patients in the U.S. The disease is characterized by cardiac problems, including heart failure, muscle weakness, fatigue, recurrent infections and delayed growth. Many patients don’t survive past the age of 5 years.

Forzinity targets an important molecule in the mitochondria, in turn boosting its activity and generating cellular energy to maintain healthy organ function.

But Forzinity’s path to approval was anything but smooth. In May, the FDA rejected the drug after it failed in a mid-stage study to demonstrate significant improvements in fatigue and motor skills versus placebo. Alongside the rejection, however, the FDA proposed that Stealth use the accelerated pathway to seek approval for the drug.

The biotech refiled last month, using an intermediate endpoint as the main basis for accelerated approval.

Forzinity’s approval covers patients weighing at least 30 kg, while leaving out children under the age of 5, who are often the most severely afflicted by Barth syndrome. Stealth’s Phase II TAZPOWER trial, on which the approval was based, only tested the drug in patients 12 years and older.

Merck Wins Nod for Subcutaneous Keytruda as LOE Approaches

The FDA on Sept. 19 approved a subcutaneous version of Merck’s blockbuster immunotherapy Keytruda, handing the pharma a win that could help it reinforce sales when the drug loses exclusivity in 2028.

The under-the-skin injection, which will carry the brand name Keytruda Qlex, is approved for “most” of the solid tumor indications as the intravenous version, Merck announced at the time of the approval. All told, Keytruda Qlex is approved for 38 cancers. The company expects to have the subcutaneous injection available in late September.

Merck has not revealed the price point for Keytruda Qlex, though a spokesperson told Endpoints News on Sept. 19 that it will be priced “at parity” to the intravenous version. According to Merck’s website, a three-week course of Keytruda costs almost $11,800.

In 2023 and 2024, Keytruda was the world’s top-selling pharmaceutical product, with earnings of $25 billion and $29.5 billion, respectively. But analysts have warned of a sales dip in the near future, particularly as key patent protections expire in 2028, making the mega-blockbuster therapy susceptible to challenge from biosimilars. Keytruda Qlex is a significant part of Merck’s efforts to soften the fall from this patent cliff.

In approving the subcutaneous version, the FDA reviewed data comparing both formulations. A pivotal study found a 45% overall response rate in non-small cell lung cancer patients treated with Keytruda Qlex versus 42% in those given the original Keytruda. Progression-free and overall survival rates were likewise similar between the two formulations.

Takeda Pushes Vonvendi Into Common Bleeding Disorder

On Sept. 5, the FDA signed off on the use of Takeda’s Vonvendi for the routine prophylaxis of adults with von Willebrand Disease (VWD), helping reduce the frequency of bleeding episodes in those with type 1 and type 2 disease. The approval also allows the use of Vonvendi for the on-demand perioperative management of bleeding in pediatric patients with VWD.

According to Takeda, Vonvendi is the only recombinant von Willebrand Factor replacement therapy indicated for both adults and children with VWD.

Afflicting more than 3 million people in the U.S., VWD is a bleeding disorder characterized by life-threatening episodes, prolonged nosebleeds and easy bruising, among other symptoms, which can greatly compromise patients’ quality of life. The disease is linked to low levels of VWF, a key protein involved in clotting.

Vonvendi addresses this deficiency by replacing missing or dysfunctional VWF. Data from three late-stage studies “showed success in treatment control of bleeding episodes” in patients of all ages, according to the FDA’s announcement of the approval. As for safety, Vonvendi’s most common adverse events included nausea, vomiting, dizziness and generalized itchiness, according to the regulator.

Before this label expansion, Vonvendi was only indicated as a perioperative on-demand therapy for bleeding episodes in adult patients, and as a preventive option only in adults with type 3 VWD, the most serious form of the disease.

FDA Clears J&J’s Drug-Device Combo for Bladder Cancer

Johnson & Johnson notched a regulatory victory for its drug-device combo Inlexzo for certain types of bladder cancer on Sept. 9.

The FDA approved the use of Inlexzo for patients with non-muscle invasive bladder cancer with carcinoma in situ who are unresponsive to Bacillus Calmette-Guérin treatment. Inlexzo can be used regardless of the presence of papillary tumors. According to J&J, Inlexzo is the first and so far only intravesical drug-releasing system that delivers an anti-cancer therapy locally into the bladder.

The approval was backed by results from the Phase IIb SunRISe-1 study, in which Inlexzo elicited an 82.4% complete response rate, according to an April readout. At one year, 52.9% of treatment responders were able to maintain undetectable levels of cancer, demonstrating what the pharma at the time called “sustained disease control.” The median duration of response was 25.8 months.

In its news release announcing the approval, J&J emphasized that Inlexzo is for patients who want to preserve their bladders.

The drug-device product comes with a urinary catheter and stylet to facilitate its insertion into the bladder. The procedure can be performed by a healthcare professional in the outpatient setting without the need for general anesthesia. There is no need for patients to be monitored in the doctor’s office after insertion.

Cortasis’ Gets Go-Ahead for Nasal Spray Loop Diuretic
The FDA on Sept. 16 signed off on Corstasis Therapeutics’ Enbumyst, the first intranasal loop diuretic indicated for edema in patients with congestive heart failure, as well as hepatic and renal disease. The company expects to make the nasal spray available in the fourth quarter.

Enbumyst’s new drug application, which the FDA accepted in January, was backed by data from a clinical trial that compared the absorption of bumetanide—the spray’s active ingredient—when given intranasally versus orally and intravenously. Results, presented last November at the American Heart Association’s 2024 Scientific Sessions, showed the nasal spray formulation could reach comparable blood level concentrations as its oral and intravenous comparators.

Variability in absorption was 27% for both the intranasal and intravenous formulations, versus 40% when given orally. This suggests that bumetanide is more stably administered via a nasal spray or an infusion.

According to Corstasis’ press announcement of the approval, the fluid overload is responsible for more than 1 million hospitalizations per year. Oral loop diuretics are effective but can be limited by poor absorption in the gut and delayed onset, while intravenous diuretics require the patient to be in a hospital or infusion center. Enbumyst, meanwhile, is self-administered in the outpatient setting.

Saol’s Ultra-Rare Disease Drug Runs into Regulatory Roadblock
The FDA on Sept. 8 rejected Saol Therapeutics’ application for SL1009, which the company was proposing for the treatment of pyruvate dehydrogenase complex deficiency (PDCD), an ultra-rare mitochondrial disease in children.

Saol did not reveal the regulator’s reasons for the rejection, only stating that the complete response letter detailed “specific observations” that the privately held biotech “will need to address to clarify the path forward.”

The company hinted, however, that it may not have the ability to resolve the issues. “To address the deficiencies as the FDA requested, it would take several years and require significant financial resources,” Saol wrote in its announcement. Currently, the biotech is working with the FDA to find a way forward for SL1009 “that does not require an additional trial.”

The rejection came as a “deep disappointment” to the United Mitochondrial Disease Foundation, a nonprofit pushing for diagnosis, treatment and cure of mitochondrial diseases. “While we fully support rigorous scientific standards, regulatory flexibility is essential for rare disease populations” like PDCD, the group wrote in an open letter.

PDCD is characterized by the toxic buildup of lactic acid in the body, resulting in what Saol calls “overwhelming health challenges.” These include nausea, vomiting, severe breathing problems, neurological impairments and an abnormal heartbeat. Most patients with PDCD do not survive beyond early childhood. There are no approved treatments for the disease.

Spinal Muscular Atrophy Space Hit With Two Rejections
Scholar Rock’s Apitegromab

Sept. 23 was a difficult day for the spinal muscular atrophy community. First, the FDA rejected Scholar Rock’s apitegromab, an investigational myostatin blocker, due to issues at a third-party manufacturer.

In particular, the regulator flagged “observations” during a routine inspection at Catalent Indiana LLC, a fill-finish site that was acquired by Novo Nordisk in December last year. “The observations are not specific to apitegromab,” Scholar Rock said in a news release on Tuesday, adding that the FDA “did not cite any other approvability concerns,” including problems with efficacy or safety.

Scholar Rock is working closely with Catalent Indiana regarding the FDA’s observations, building up to a resubmission “as soon as possible,” CEO David Hallal said in the company’s announcement. The biotech has not yet provided specific timing for its resubmission.

The rejection did not come as a surprise to BMO Capital Markets. In a note to investors, BMO analysts said the FDA’s decision was “in line with our expectations,” nevertheless noting that the uncertain timing of Scholar Rock’s refiling “could create more downside” to the company’s shares. Still, the lack of issues with apitegromab’s data package is a “mild positive” for Scholar Rock, BMO added, writing that this could “mitigate further concerns” surrounding the rejection.

To support its application for apitegromab, Scholar Rock filed data from the Phase III SAPPHIRE study, which in October 2024 demonstrated a significant improvement in motor function. Benefits were apparent as early as eight weeks and further improved through 52 weeks of follow-up, the company said at the time.

Biogen’s High-Dose Spinraza

The same day, the FDA denied approval for a higher-dose formulation of Biogen’s antisense oligonucleotide Spinraza for spinal muscular atrophy.

Biogen’s rejection was likewise linked to manufacturing concerns. In its news release on Sept. 23, the company noted that the regulator asked for updated technical information in the chemistry manufacturing and controls portion of the application. The FDA did not identify problems with Biogen’s clinical data package for high-dose Spinraza (nusinersen).

The company is working to address the agency’s requests and plans to refile the application “promptly,” according to the press announcement.

“Given the limited scope of updates required and lack of efficacy concerns raised, we see no true concerns to high-dose nusinersen’s ultimate approval,” analysts at BMO Capital Markets told investors in a Sept. 23 note, adding that the FDA’s issues pose a “quickly resolvable setback” for Biogen.

Spinraza’s active ingredient is the antisense oligonucleotide nusinersen, which works by promoting the production of the SMN protein, which is typically deficient in patients with spinal muscular atrophy. The drug was approved in 2016 for this condition, though its current regimen involves a 12-mg dose with an induction schedule involving four loading doses. Biogen’s proposed higher-dose formulation uses two 50-mg intrathecal injections for initiation, followed by 28-mg maintenance doses.

Data from the Phase II/III DEVOTE study showed that the investigational formulation of Spinraza elicited significantly higher improvements in motor skills as compared with a sham control. Higher-dose Spinraza also outperformed the standard-dose formulation, though the effect fell short of significance.

Changes in the political climate of the United States are spilling into scientific research. While many past administrations, of both parties, supported and funded science funding and education, the current administration has enacted cuts to currently funded research upwards of 40% and the proposed budget for the 2026 fiscal year shows a 39.3% cut to NIH funding.

While this may not be initially concerning to most people who may ask how this could possibly impact their daily lives—it is a pressing concern when one considers the broader impacts of reduced research funding.

“Recently, when asked to assess how large NIH reductions would affect drug development, the Congressional Budget Office reported that its data and methods did not permit an estimate,” wrote the authors.

To quantify exactly what the impacts on biomedical research and innovation the reduced NIH funding might have, researchers at the Massachusetts Institute of Technology (MIT) and Johns Hopkins University conducted an analysis of the publications cited in small-molecule drug patents to determine how many NIH funded projects were involved in the discovery and development of those drugs.

Their study, “What if NIH funding had been 40% smaller?” is published as a Policy Article in Science.

The NIH uses priority lists in determining funding status of project applications. Utilizing priority lists allowed the researchers to identify studies that were in the lower 40 percent of the NIH-funded projects based on priority. They dubbed these studies as “at-risk” projects based on the current and proposed funding cuts.

“The indirect connection is where we see the real breadth of NIH’s impact,” said coauthor Danielle Li, an economist at MIT. “What the NIH does is fund research that forms the scientific foundation upon which companies and other drug developers build.”

Analyzing data from priority lists covering the period from 1980 though 2007 in conjunction with new molecular entities (NMEs) approved by the FDA between 2000 and 2023, the researchers aimed to cover the time span that it takes for basic research to progress to drug development.

The team surmised that “if few advances are connected to at-risk grants, it would suggest that a 40% NIH budget cut might have had limited consequences for drug development, implying less cause for concern about current proposed reductions.” However, if the patents have a strong basis in NIH-funded research, the opposite would hold true and the current concern would be validated.

At-risk grants were linked to NMEs both directly and indirectly. Direct connections included patents that explicitly acknowledge support from at-risk grants via their “government interest statements,” while indirect links were patents that included citations which acknowledged at-risk grants.

The team identified 557 drugs that were approved by the FDA between 2000 and 2023. Of these, 40, or 7.1%, directly acknowledged NIH-funding, and 14 acknowledged funding coming from an at-risk grant. Meanwhile, 331 drugs, 59.4%, were indirectly connected to NIH support, meaning that these patents cited at least one NIH-funded project. More than half of the drugs, 286 (51.4%) were connected to at-risk grants.

“What we found was quite striking,” said Li. “More than half of the drugs approved by the FDA since 2000 are connected to NIH research that would likely have been cut under a 40 percent budget reduction.”

There are many nuances to this work, which the authors acknowledge—some indirect research may have been pivotal to the development of a drug, but conversely, just because a NIH-funded paper is cited, doesn’t mean it was a linchpin. However, there were clear cases of direct links between at-risk grants that led to drug development.

Further, while this report shows a substantial impact of NIH funding on small-molecule drug development in the U.S., it is limited in its scope. Medical devices, vaccines, cell and gene therapies, diagnostics, and other biomedical therapies and practices were excluded in the present study. Inclusion of these missing pieces may show a higher impact of reduced funding on biomedical innovations.

The authors also point out that they were “unable to identify the (likely many) scientists whose careers would have been cut short without NIH support during their doctoral and postdoctoral studies.”

“The worry is that these kinds of deep cuts to the NIH risk that foundation and therefore endanger the development of medicines that might be used to treat us, or our kids and grandkids, 20 years from now,” Li said.

New research in C. elegans from scientists at Howard Hughes Medical Institute (HHMI) helps explain how changes in the parents’ lysosomes that promote longevity are transferred to their offspring. Their findings are detailed in a new Science paper titled “Lysosomes signal through the epigenome to regulate longevity across generations.”

The work comes out of the laboratory of Meng Wang, PhD, a senior group leader at HHMI’s Janelia Research Campus. Previous research from the Wang lab showed that overexpressing a particular enzyme in C. elegans lysosomes extended its life by up to 60 percent. Surprisingly, offspring from these worms that did not have the genetic modification as their parents also lived longer than normal. And when these long-lived worms were crossed with wild-type worms that did not have the same modification, offspring from those unions also lived longer.

Based on these findings, the researchers hypothesized that the longevity markers were somehow being transferred across generations. Their latest study in Science sheds some light on how this might be happening. According to the paper, Wang and her team found that the changes in C. elegans lysosomes are transferred to its reproductive cells via histones. In reproductive cells, these histone messengers modify the worm’s epigenome, enabling the lysosomal changes to be passed through the generations without changing the underlying DNA.

“You always think that your inheritance is in the nucleus, within the cell, but now we show that the histone can go from one place to another place, and if that histone carries any modification, that means you are going to transfer the epigenetic information from one cell to another,” Wang said. “It really provides a mechanism for understanding the transgenerational effect.”

Specifically, the scientists identified a specific histone modification was elevated in the worms that lived longer compared to those with normal lifespans. Then using a combination of tools including transcriptomics and imaging, they found that changes in lysosomal metabolism, which are activated during fasting, kick off a series of processes in the cells which triggers an increase in a specific histone variant. That histone is then transported to the reproductive cells via proteins, where it is modified in a way that allows the lysosomal information to enter the germline where it can be transferred from parent to offspring.

Besides conferring longevity across generations, the team believes that this mechanism could help explain how other types of inherited information is passed from parent to offspring in C. elegans. For example, the findings could help researchers better understand previously observed transgenerational effects like the malnutrition of a parent affecting its offspring, or how epigenetic modifications for coping with environmental stress can be passed from parents to offspring.

Changes in the political climate of the United States are spilling into scientific research. While many past administrations, of both parties, supported and funded science funding and education, the current administration has enacted cuts to currently funded research upwards of 40% and the proposed budget for the 2026 fiscal year shows a 39.3% cut to NIH funding.

While this may not be initially concerning to most people who may ask how this could possibly impact their daily lives—it is a pressing concern when one considers the broader impacts of reduced research funding.

“Recently, when asked to assess how large NIH reductions would affect drug development, the Congressional Budget Office reported that its data and methods did not permit an estimate,” wrote the authors.

To quantify exactly what the impacts on biomedical research and innovation the reduced NIH funding might have, researchers at the Massachusetts Institute of Technology (MIT) and Johns Hopkins University conducted an analysis of the publications cited in small-molecule drug patents to determine how many NIH funded projects were involved in the discovery and development of those drugs.

Their study, “What if NIH funding had been 40% smaller?” is published as a Policy Article in Science.

The NIH uses priority lists in determining funding status of project applications. Utilizing priority lists allowed the researchers to identify studies that were in the lower 40 percent of the NIH-funded projects based on priority. They dubbed these studies as “at-risk” projects based on the current and proposed funding cuts.

“The indirect connection is where we see the real breadth of NIH’s impact,” said coauthor Danielle Li, an economist at MIT. “What the NIH does is fund research that forms the scientific foundation upon which companies and other drug developers build.”

Analyzing data from priority lists covering the period from 1980 though 2007 in conjunction with new molecular entities (NMEs) approved by the FDA between 2000 and 2023, the researchers aimed to cover the time span that it takes for basic research to progress to drug development.

The team surmised that “if few advances are connected to at-risk grants, it would suggest that a 40% NIH budget cut might have had limited consequences for drug development, implying less cause for concern about current proposed reductions.” However, if the patents have a strong basis in NIH-funded research, the opposite would hold true and the current concern would be validated.

At-risk grants were linked to NMEs both directly and indirectly. Direct connections included patents that explicitly acknowledge support from at-risk grants via their “government interest statements,” while indirect links were patents that included citations which acknowledged at-risk grants.

The team identified 557 drugs that were approved by the FDA between 2000 and 2023. Of these, 40, or 7.1%, directly acknowledged NIH-funding, and 14 acknowledged funding coming from an at-risk grant. Meanwhile, 331 drugs, 59.4%, were indirectly connected to NIH support, meaning that these patents cited at least one NIH-funded project. More than half of the drugs, 286 (51.4%) were connected to at-risk grants.

“What we found was quite striking,” said Li. “More than half of the drugs approved by the FDA since 2000 are connected to NIH research that would likely have been cut under a 40 percent budget reduction.”

There are many nuances to this work, which the authors acknowledge—some indirect research may have been pivotal to the development of a drug, but conversely, just because a NIH-funded paper is cited, doesn’t mean it was a linchpin. However, there were clear cases of direct links between at-risk grants that led to drug development.

Further, while this report shows a substantial impact of NIH funding on small-molecule drug development in the U.S., it is limited in its scope. Medical devices, vaccines, cell and gene therapies, diagnostics, and other biomedical therapies and practices were excluded in the present study. Inclusion of these missing pieces may show a higher impact of reduced funding on biomedical innovations.

The authors also point out that they were “unable to identify the (likely many) scientists whose careers would have been cut short without NIH support during their doctoral and postdoctoral studies.”

“The worry is that these kinds of deep cuts to the NIH risk that foundation and therefore endanger the development of medicines that might be used to treat us, or our kids and grandkids, 20 years from now,” Li said.

Synaffix, a Lonza company focused on commercializing its clinical-stage platform technology for the development of antibody-drug conjugates (ADCs), entered into a licensing agreement with Qurient, a clinical-stage biopharmaceutical company based in South Korea, for the development of a dual-payload ADC.

Dual-payload ADCs are designed to deliver two separate cytotoxic agents with distinct mechanisms of action to target cancer cells, aiming to enhance therapeutic efficacy and mitigate payload resistance. Their therapeutic promise can potentially expand the current range of effective treatments while minimizing toxicity to healthy tissues, especially in refractory cancer cases.

The collaboration aims to develop a dual-payload ADC consisting of Synaffix’s exatecan-based technology and Qurient’s CDK7 inhibitor, aiming to target unmet medical needs in solid tumors. Under the terms of the agreement, Qurient will gain access to Lonza’s clinical-stage, site-specific ADC technology platform powered by Synaffix services, including GlycoConnect® antibody conjugation, HydraSpace® polar spacer, and exatecan-based linker-payload technologies, as well as Lonza’s expertise and experience in developing and manufacturing bioconjugates.

Lonza will manufacture components related to its proprietary Synaffix technologies, and Qurient will perform the R&D, development, manufacturing, and commercialization of the ADC, and manufacturing of Qurient’s CDK7 inhibitor.

“This licensing collaboration with Qurient signifies the versatility of our ADC platform technology. Enabling the development of a dual-payload ADC built with Synaffix technology reflects our drive to continue pioneering innovation in the field,” said Peter Van de Sande, head of Synaffix.

“Dual-payload ADCs represent the next frontier in targeted antibody therapeutics, and we look forward to advancing this novel combination of our CDK7 inhibitor and Synaffix’s SYNtecan™ linker-payload,” added Kiyean Nam. “The combination of our proprietary technology with Synaffix’s platform has the potential to be applicable to a wider range of targets and antibodies.”