BOSTON — Thomas Bartlett’s life changed in 2019 when he was diagnosed with late-onset myasthenia gravis (MG). The 15-year veteran of the Bio-IT World Conference and Expo took to the stage on Tuesday as one of seven speakers in the opening plenary session of this year’s conference, which focused on various aspects of rare disease research and treatment.   

The session offered a poignant, but often uplifting, launch to the annual conference, which celebrated 25 years from its inception in 2002, when the event was produced by the IDG World Expo Group.   

Speaking with Susan Ward, PhD, founder and executive director of the Collaborative Trajectory Analysis Project (cTAP), Bartlett described an active life and fulfilling work prior to his diagnosis, and some of the debilitating physical and emotional impact of his disease. “I have to plan everything. If I’m going to go out, I plan ahead of time where I’m going to go [and] the amount of time,” he said. “I have to plan recovery.” Bartlett’s MG has prevented him from working a full-time job, as he would need a full day of rest just to recover from each day. “The math doesn’t work.” 

Bartlett is now an ambassador for MG United Myasthenia Gravis, an online platform designed to support some 70,000 patients living with the disease in the United States alone. Though there are some treatments that alleviate disease symptoms, there currently is no cure. Bartlett’s disease was diagnosed early thanks to a quick-thinking primary care provider. A recurring theme in the session was the stark reality that many in the rare disease community wait many years for a diagnosis.   

Of the estimated 7–8,000 rare genetic diseases, many not well understood. About one in 10 people in the U.S. “either has or will have a rare disease at some point,” Ward noted. In a conference of about 2,700 attendees, “there are going to be about 270 people on average who might have a rare disease. So the magnitude of the problem is huge, even though the numbers of people are quite small.”  

Given the computational nature of the Bio-IT conference, Bartlett and Ward soon turned to data and the challenges with collecting and aggregating information from rare disease populations. Ward noted that centers of excellence in rare disease may have several patients but “no one center that has enough data for anybody to really learn much.” Aggregating data from multiple centers and across geographies is one possibility but due to the differences that exist between centers across states and countries, “you need a really rich and deep ontology” as well as “context for what those data mean,” she said.   

And that’s not the only challenge. In many cases, rare diseases can present and progress differently in patients with the same condition. “Imagine you’re trying to design a clinical trial. You’ve got patients who are fluctuating [while] you’re really looking for patients who are slowly declining” and “patients who have intermittent remissions,” Ward noted. With that mix, “you’re going to have a very noisy trial.”   

There are also other data sources that could provide value. Bartlett noted that wearable devices such as the Apple watch capture useful health-related data, but as it is not clinical data, physicians cannot use it. As someone with decades of tech experience—including a stint at Apple—Bartlett asked: “How do we change that?” How do we prove the patient’s experience with the data that we can collect, and work with companies and legislation” to “include real world data and evidence and compare that … with the clinical data and get a much broader picture.”   

Bartlett’s closing comments focused on hope for people living with rare diseases. And with good reason given recent successes in development of gene therapies and other therapeutics. As a patient, “you need to have something that you can look forward to today,” he said. For now, MG is incurable but “we will find ways to get to that end game and ultimately have a cure or at least a high level of quality of life.” 

Shortening the rare disease diagnostic journey 

Sebastien Lefebvre, head of technology, data and AI at Aurelis Insights, has spent 10 years in the rare disease space in different capacities including developing platforms for digital decision support or “data-driven and AI-assisted support decisions.” Speaking with William Van Etten, PhD, co-founder, CEO and principal scientist, StarfleetBio, Lefebvre described Rare Answers, a clinical decision support platform for rare disease diagnostics that he worked on while at Alexion Pharmaceuticals. The platform was designed in collaboration with two children’s hospitals as well as a number of technology and data science companies. 

He also described a second project in 2022 with the Rare-X program that analyzed data from public databases of rare and inherited diseases, drugs, and genes. Lefebvre and his colleagues hoped to produce an accurate assessment of the total number of rare diseases. Following extensive data cleaning and normalization—now made much simpler with advances in AI and machine learning—they arrived at a figure closer to 12,000. Of that number, between 80–87 percent have a genetic basis and about 80 percent had at least three associated phenotypic descriptors. That kind of information provides a viable starting point for applying AI-assisted data-driven diagnostic approaches. This is important because, as Bartlett noted, many patients with rare diseases wait years for a diagnosis. “It all starts with a diagnosis,” Lefebvre said. “[If] you don’t known what you’ve got, how can you [treat it].” 

Van Etten is focused on making individual genomes truly private. The emergence of commercial personal genomics companies created a data privacy problem. Customers pay for their genomes to be sequenced by a company that holds the data, reads it, and sends periodic reports. He has developed an app called DNAVault that lets people host their genomes on their smartphones, putting data control back into their hands.  

Van Etten’s new company, StarfleetBio, is partnering with his former consulting firm, BioTeam, and the Hubbard Center for Genomic Studies at the University of New Hampshire, to provide sequencing services. 

“It used to be that we needed to centralize all the human genome data because you need a lot of compute to perform the analysis, but it’s really not required anymore,” he said. “We decided to decentralize it, where your genome is on your phone, you can generate your own reports, and nobody has access to it but you.”  

Each encrypted genome is only accessible with a key unique to the individual’s phone. This way, only they individual can download their data and read it. Some audience members clearly approved of Van Etten’s app, with shouts of “Bravo!” from the back of the hall. (The app was later named one of three “Best of Show” winners at this year’s meeting.)  

Among the features in the app is a fun kinship feature, which lets two people determine if they are related by placing their phones in close proximity as if sharing a Wi-Fi password. Another feature dubbed “origins” lets people track their ancestry over thousands of years via their Y-chromosome or mitochondrial DNA. Van Etten was particularly moved by the kind of insights this feature revealed about human relationships. “We found that all humans are far more closely related than we thought,” he said. “We all really [came from] the same 5,000–10,000 people from 50,000–70,000 years ago.”   

Another app feature screens for the 81 ACMG medically actionable genes to provide health reports, while a final feature lets people ask questions about their genome and get answers much the same way one might enter a question into Google or ChatGPT.  

Tying this to rare diseases, Van Etten is working on ways for app users to opt into participating in relevant research studies and clinical trials. The idea is that users could “toggle a switch” that would let alert the relevant researchers and then answer questions to help gauge eligibility. Importantly, this would all be done without people having to share their primary information.   

Learning from rare diseases to treat common conditions 

Another plenary conversation took place between Morgan Cheatham, MD, partner, head of healthcare & life sciences, Breyer Capital, and Catherine Brownstein, PhD, manager of the Molecular Genomics Core Facility at Boston Children’s Hospital and scientific director of the Manton Center for Orphan Disease Research Gene Discovery Core.   

Brownstein and Cheatham use OpenAI’s generative AI to help diagnose patients who in some cases had been waiting decades for answers. Importantly, “this was a zero-shot model,” Cheatham noted. “We didn’t do any specialized training of GPT-3, we just deployed the existing models and we’re able to return answers to families who have been waiting for sometimes over a decade.” 

 He also acknowledged the contributions of people living with rare diseases to many major drug modalities including CAR Ts and RNA medicines. “Many of those modalities were actually validated” with “the help of rare patients who were willing to participate in trials that allowed us to show the efficacy, the safety, and the durability of these modalities.”  

According to Brownstein, a deeper understanding of rare conditions often has implications for more common conditions. “As someone who spent six years studying hypophosphatemic rickets …  it’s these extreme cases, these rare presentations of disorders where you don’t know the underlying etiology [that] inform the common diseases,” she said. Understand the biology behind hypophosphatemic rickets “has implications for bone density and osteoporosis that affects a ton of us in this room.”  

Many opportunities were highlighted where some form of AI is already being used or could be applied. One company that Cheatham mentioned is applying AI to colonoscopies to characterize inflammation levels in the bowel in a standardized way with an eye towards connecting patients with ulcerative colitis and Crohn’s disease to relevant clinical trials. There are also opportunities in cardiology, neurology, pathology and more.    

Giving more patients the right to try 

In the closing conversation, Van Etten spoke with Dylan Livingston, founder and president of The Alliance for Longevity Initiatives (A4LI). Livingston is at the forefront of efforts aimed at implementing policies in different states that allow patients with rare diseases to try treatments that may benefit before they have been approved.

The story of how Livingston, still in his 20s, got involved in healthcare policy is interesting. As a college senior during the Covid-19 lockdowns, “I started thinking about COVID as it relates to age [and] why … [I] would be pretty much completely unaffected by COVID and why my grandfather at 92 would most likely die,” he recalled. “It all comes back to aging, your immune response to these diseases and your immune response to chronic diseases overall.” That got him interested in the field of aging and longevity more broadly. 

Livingston and his group have worked to pass laws in the state of Montana that extend eligibility under the Right to Try Act, a piece of federal legislation that lets people with terminal illnesses try therapeutics that may help them which are not yet fully approved. The issue with the Right To Try Act as it stands is that “the definition of who is eligible is very narrow” and restricted to people with months left to live “which made no sense to me” Livingston said. From his perspective, people just diagnosed with conditions like Alzheimer’s or Parkinson’s should also have the chance to access treatments which could potentially help them earlier in their journeys as those who are further along in their journeys.  

Expanding the Right to Try provides a possible pathway to those treatments without requiring approval from the U.S. Food and Drug Administration, which may be years away.  

Livingston and his team have been successful in expanding the law in Montana to cover people with age-related ailments as well as people with rare diseases, people recently diagnosed with terminal diseases, and people with disease that will eventually become terminal. Now he and his team are working on getting similar changes in place in New Hampshire. There are safeguards in place: the proposed treatment has to be prescribed by two physicians, pass through IRB review, and the therapy must have passed a Phase I testing. “What we’re trying to do is create a system that is safe enough to prevent as many tragedies as possible while also opening up access to as many people as possible,” Livingston said.    

As an example of the benefit of changing the law, Livingston shared a story of a father whose son had died from a rare mitochondrial disease. The father has since had the genomes of his two other children sequenced, only to discover that they carry the same mitochondrial mutation. In this scenario, Montana’s model would allow the father in this instance to bypass the strict requirements of a drug trial and access treatments that could potentially help his children. 

“Maybe it’s not as great in terms of a data collection standpoint for companies, but what we’re offering here [are] options for people that don’t have any other options.”   

Many scientists first encountered G protein–coupled receptors (GPCRs) as a looping sketch across the cell membrane in an early biology textbook. That simple diagram belied the complexity of a receptor family now known to govern vision, smell, hormone sensing, and the actions of countless medicines. Yet despite their centrality, designing molecules that can precisely switch GPCRs on or off has remained one of drug discovery’s most persistent challenges.

A new study led by the UW Medicine Institute for Protein Design and Skape Bio demonstrates that AI‑driven de novo protein design can finally meet that challenge. The work, published recently in Nature, shows that computationally designed miniproteins—compact proteins under 100 amino acids—can be engineered to either activate or block GPCRs with high affinity, potency, and selectivity. The paper is titled “De novo design of miniproteins targeting G protein-coupled receptors.”

The research team developed a suite of design strategies to create miniproteins capable of slipping into the deep, flexible pockets that govern GPCR signaling. These pockets shift shape depending on whether the receptor is active or inactive, making them difficult to target with conventional biologics. By designing molecules that recognize specific receptor states, the team generated agonists for receptors involved in itch and pain, and antagonists for receptors implicated in cancer, metabolic disease such as diabetes and obesity, and migraine.

“Protein design takes our understanding of how proteins fold and reverses it—asking if we can envision, with the aid of AI computing, a new protein that sticks to a target in a purpose-built way,” said senior author David Baker, PhD, director of the Institute for Protein Design, professor of biochemistry at the University of Washington School of Medicine, and a Howard Hughes Medical Institute Investigator. “This paper showcases how we can do this repeatedly for different GPCRs in ways that capitalize on their dynamic motion to either activate or inactivate them.”

Cryo‑EM structures of five designed miniproteins closely matched their computational models, underscoring the accuracy of the design pipeline. In one mouse study, a designed chemokine‑receptor antagonist mobilized hematopoietic stem and progenitor cells at levels comparable to a clinically used drug—but with fewer side effects, according to the authors.

For first author Edin Muratspahić, PhD, the moment of validation came when the designed molecules did more than bind. “Seeing computationally designed miniproteins not only bind but actually control GPCR signaling in living cells was a defining moment for me,” he said.

A second major advance reported in the study is a high‑throughput “receptor diversion” screening system that evaluates tens of thousands of designed proteins directly in living human cells. Traditional GPCR screens often require purifying or stabilizing receptors—steps that can distort their natural signaling behavior. By keeping receptors in their native membrane environment, the new system accelerates discovery while preserving biological relevance.

According to corresponding author Christoffer Norn, PhD, co‑founder of Skape Bio, the study lays out a roadmap for all‑computational design of GPCR ligands.

The methods described in the paper are already being adapted at Skape Bio to explore GPCR targets involved in metabolic, inflammatory, and neurologic pathways—areas where conventional discovery efforts have often struggled.

The agreement is the largest in a series of deals that Gilead Sciences has penned with Korea’s Yuhan.

Gilead Sciences has struck a $139.8 million deal to source ingredients from Yuhan, expanding its long-standing relationship with the South Korean manufacturer.

The value of the agreement, which was reported by Korea Biomedical Review, amounts to almost 10% of Yuhan’s sales for last year. The contract started May 19 and is scheduled to run until the end of next year. Yuhan’s disclosure lacks details of which active pharmaceutical ingredients (APIs) it will supply to Gilead under the terms of the deal.

Gilead has a history of sourcing antiviral APIs from Korean manufacturers. In the 2010s, ST Pharm supplied APIs for Gilead’s hepatitis C drugs. Later, Yuhan landed a $45.3 million deal to supply API for Gilead’s HIV drugs in 2018. Gilead struck another deal with Yuhan for HIV APIs in 2024, agreeing to pay $80.9 million for the ingredients. The 2024 deal coincided with a period when U.S. companies were moving API production out of China in anticipation of the Biosecure Act.

Gilead’s latest deal with Yuhan is the second API supply agreement with a U.S. biopharma that the Korean manufacturer has disclosed this month. Earlier in May, Yuhan revealed a $38.1 million contract to supply BridgeBio Pharma with API for a cardiomyopathy treatment. BridgeBio sells the transthyretin amyloid cardiomyopathy therapy Attruby.

Yuhan’s compatriot ST Pharm has reported two deals worth more than $50 million this year. In January, the company disclosed a roughly one-year, $56.3 million agreement to supply APIs to the U.S. to support commercialization of an oligonucleotide treatment for severe hypertriglyceridemia. ST Pharm reported another oligonucleotide deal in March, this time a $59.9 million European pact.

The orders are supported by capacity expansions, Seoul Economic Daily reported. Yuhan completed the expansion of one plant in April and plans to expand another building at the same site, with construction set to start this year and a view toward commencing operations in the first half of 2028. ST Pharm completed construction of a second oligonucleotide building last year.

Going private could give Recordati strategic flexibility and a stable source of capital, according to CVC Capital Partners and Groupe Bruxelles Lambert, which are offering to take the Italian pharma private for a 13% premium.

Recordati has received a massive offer from a pair of investment firms to take the Italian pharma giant off the public market and move forward as a privately-held drug developer.

The firms are offering €51.29 (around $59.5) per Recordati share, representing a 13% premium to the pharma’s closing price in March, when one of the bidders—CVC Capital Partners—first expressed its acquisition intent, according to a Friday news release. If it pushes through, the takeover could reach €10.73 billion in value, or approximately $12.44 billion.

Alongside CVC is Groupe Bruxelles Lambert (GBL), a public investment holding company.

Recordati is “now entering a new phase of development, characterized by a number of strategic opportunities ahead,” the bidders wrote on Friday, contending that this exposes the pharma to “greater execution risk, longer development timelines and increased R&D investment.”

Going private will help Recordati as it enters this new phase of its business, the letter added, “providing strategic flexibility, stable capital base and aligned long-term shareholder support.”

In conjunction with Friday’s offer, Rossini—a company controlled by CVC and which holds 46.82% of Recordati’s share capital—has agreed to tender its shares to the prospective buyers. The offer, if it pushes through, would close in the fourth quarter of 2026, according to the press announcement.

Recordati’s go-private offer continues what PitchBook Senior Biotech Analyst Kazi Helal calls the “PE-ization of pharma,” referring to private equity firms. Over the past year or so, there has been a trend of biopharma companies increasingly turning toward private money to keep their drug development engines chugging along.

Private equity investors “are seeing opportunity now in biotech and distressed assets, and it’s hard to pass off,” Helal told BioSpace in July 2025. Meanwhile, many biotechs are struggling and could use an infusion of private money.

Arguably the most notable example of this deal type is bluebird bio, which was acquired by private firms Carlyle and SK Capital Partners for around $50 million last year.

A less extreme case is Lexeo Therapeutics, which in June 2025 secured $40 million in backing from Perceptive Xontogeny Venture Funds and venBio Partners to advance its gene therapies for cardiovascular diseases.

There’s also Anthos Therapeutics, which launched in February 2019 with $250 million from Blackstone Life Sciences and a blood thinner candidate from Novartis dubbed abelacimab. In February last year, Novartis decided it wanted its asset back and absorbed Anthos for $3.1 billion.

Lilly met analysts’ sky-high expectations with 28.3% weight loss over 80 weeks for the triple hormone receptor agonist retatrutide in a highly anticipated readout on Thursday.

People taking Eli Lilly’s next-gen weight loss drug retatrutide lost an average of 70 pounds, or 28.3% weight loss over 80 weeks—an amount typically seen with bariatric surgery, the pharma and analysts said. The results have heaped more credence to the triple hormone receptor agonist’s “supremely strong” profile, according to analysts.

There’s “a new sheriff in town,” BMO Capital Markets quipped on Thursday morning after the results were released.

Truist Securities analysts echoed that excitement. “We believe these data set a new benchmark for anti-obesity medications and will support retatrutide approval and use in patients that are not adequately served with existing incretin options,” the group wrote on Thursday. The firm provided a conservative worldwide peak sales estimate of between $12 and $19 billion, given that retatrutide will likely be reserved for more severe cases of obesity. BMO anticipates a 2027 launch.

The late-stage results from the TRIUMPH-1 study of patients with obesity but not diabetes easily met analysts’ sky-high expectations for the triple hormone receptor agonist. Prior to the Thursday readout, BMO Capital Markets had been expecting weight loss in the range of 27% to 28.5%.

The study examined 4-mg, 9-mg and 12-mg doses. In the latter two groups, weight loss was 25.9% (64.4 pounds) and 28.3% (70.3 pounds), respectively, according to a Thursday release. The low dose, which featured just one dose-escalation step, saw weight loss of 19%, or 47.2 pounds. The study met its primary endpoint of percent change in body weight at 80 weeks.

The placebo-adjusted rate in the high-dose arm was 26.1%, according to BMO’s calculations. This is slightly lower than the 26.6% Lilly reported in the previous TRIUMPH-4 trial but still helped validate the therapy, according to the analysts. The slightly worse result could stem from differences in enrollment, as the TRIUMPH-4 study focused on patients with obesity and osteoarthritis.

The 12-mg group also saw 65.3% of participants achieve a body mass index (BMI) under 30, below the threshold of obesity. For participants starting with a BMI above 40, 37.5% of individuals achieved this milestone.

Improving uptake

The earlier TRIUMPH-4 readout was heralded as a success but did reveal a safety signal called dysesthesia, a neurological condition that causes normal sensations to feel unusual or painful.

The same was shown in the TRIUMPH-1 trial. Rates of dysesthesia rose along with the dose, with 12.5% of patients experiencing the sensation in the 12-mg arm. Patients taking the drug also experienced higher rates of urinary tract infections as compared to the placebo group. Lilly said these events were mild to moderate.

BMO was encouraged by slightly improving rate of dysesthesia and gastrointestinal adverse events. The “slightly lower weight loss is countered with improved safety profile,” the analysts wrote.

“While some investors may have expected better weight loss relative to TRIUMPH-4, we view retatrutide’s significantly improved discontinuation rate and rates of dysesthesia as a positive that is likely to improve uptake when eventually commercialized,” BMO said.

Discontinuation rates were greater with the higher dose group, with 11.3% stopping treatment in the 12-mg arm compared with 4.9% on placebo. In the lowest dose group, just 4.1% of participants discontinued treatment.

Some patients in TRIUMPH-1 with a BMI above 35 on the 12-mg dose continued into an extension phase, losing 85 pounds (30.3% of body weight) at 104 weeks. Lilly also noted improvements in cardiovascular risk factors such as waist circumference, cholesterol and blood pressure.

Better than surgery

Kenneth Custer, president of Lilly Cardiometabolic Health, said the results across dose groups show that retatrutide can be tailored to each patient. The therapy “delivered a level of weight loss long associated with bariatric surgery,” which has long been a standard—although highly invasive—treatment for severe obesity.

BMO concurred with this assessment, suggesting that the low dose provides an option for patients that want “a lower strength presentation of the therapy.”

Truist also backed the bariatric surgery statement, noting that the drug “can consistently deliver weight loss that approximates bariatric surgery levels.”

Lilly did not provide an estimate for FDA filing with the readout, but BMO suspects the data will help support a new drug application later this year.

The pharma plans to present more data from TRIUMPH-1 at the American Diabetes Association Scientific Sessions in June, and will have readouts from other studies in the TRIUMPH program later in the year.

Lilly’s shares were slightly elevated at about $1,024 apiece in pre-market trading on Thursday morning.

Researchers headed by a team at Icahn School of Medicine at Mount Sinai have discovered that many gut bacteria use a flexible survival strategy—known as epigenetic “bet-hedging”—to withstand disruptions such as antibiotics and diet changes.

Studying infant and gut microbiomes, the investigators showed that microbes can switch between functional states, rather than relying solely on genetic mutations, to try to survive shifting conditions. While bet-hedging has been observed in disease-causing bacteria, this is the first study to show that it is widespread among the beneficial microbes that make up the healthy human gut.

The findings shed light on a previously hidden layer of microbiome biology and may help explain why probiotics and fecal microbiota transplantation (FMT) produce inconsistent benefits across individuals.

Gang Fang, PhD, professor of genetics and genomic sciences and director of the Center for Genomic AI and Microbiome Medicine at the Icahn School of Medicine at Mount Sinai, is senior and corresponding author of the team’s published paper in Cell Host & Microbe, titled “Epigenetic phase variation in the gut microbiome enhances bacterial adaptation.”

The human gut microbiome is constantly being disturbed—by medications, illness, and shifts in diet. Yet it often rebounds, the investigators noted. “In response to these alterations, the gut microbiome shows a remarkable adaptive capacity,” they wrote. “Characterizing this adaptive capacity is crucial for understanding the dynamic relationship between the gut microbiome and host physiology, especially in the context of human health and disease.”

Until now, scientists largely attributed this resilience to genetic mutations that accumulate over time. But, as the authors continued, “Another mechanism of bacterial adaptation involves DNA methylation, which can regulate gene expression, enhance clonal heterogeneity, and mediate epigenetic phase variation (ePV, intra-strain epigenetic variation that leads to phenotypic differences … ePVs have been characterized in human pathogens, but their roles in commensals remain unclear.”

Fang continued, “Our study shows that there is another mechanism at work. Even within a single group of genetically identical bacteria, a small subset of cells exists in a different epigenetic state—where chemical tags on the DNA change how genes are turned on or off without altering the genetic code itself. That means some cells are essentially preprogrammed to respond differently to stress, giving the population a built-in survival advantage when conditions suddenly change.”

So when a stressor such as an antibiotic is introduced, this small subgroup can quickly become dominant because it is already primed to survive. When conditions change again, the population can shift back. This reversible strategy, known as “bet-hedging,” allows microbial communities to adapt rapidly to uncertainty.

To carry out their work, the researchers combined advanced DNA sequencing, large-scale data analysis, and laboratory experiments. They used long-read sequencing technology to analyze stool samples from infants before and after antibiotic treatment, as well as from FMT donor-recipient pairs. This approach allowed them to detect both genetic structure and epigenetic modifications simultaneously.

The scientists then analyzed more than 2,300 microbiome samples from previously published studies to determine how common this phenomenon is across individuals and bacterial species. To understand the mechanism in detail, the team isolated a beneficial gut bacterium, Akkermansia muciniphila, and tracked how its epigenetic states shifted in response to different antibiotics—identifying a specific gene involved in the process.

“Focusing on an Akkermansia muciniphila isolate, we find a specific ePV regulating mucC, a gene of unknown function but whose heterologous expression enhances bacterial tolerance to antibiotics via a bet-hedging strategy,” they stated. “Our results indicate that in the human gut, ePVs may help bacterial populations regain heterogeneity after bottlenecks encountered during colonization of a new host or severe perturbations due to antibiotic exposures.”

“Our work is the first to systematically demonstrate epigenetic bet-hedging across the human gut microbiome,” Fang noted. “It also identifies a specific gene that controls this switch in a beneficial bacterium and shows that the process is reversible—shifting in different directions depending on the type of antibiotic exposure. We were struck by how quickly small subpopulations could take over. In some cases, bacteria representing less than one percent of a population became dominant under changing conditions.”

The research team also found significant diversity within what had been considered a single bacterial strain. Even closely related cells could behave differently, with distinct gene activity and stress responses—highlighting how much remains to be understood about the microbiome at a deeper level. The findings help explain why the microbiome is resilient yet difficult to predict, and why microbiome-based treatments can produce variable results.

“At the same time, our study does not suggest that people should avoid antibiotics when they are medically necessary, nor does it recommend for or against any specific probiotic. Our research is aimed at understanding fundamental biology, not changing current medical care,” added Fang.

“Compared with genetic phase variation, ePV offers several advantages in enhancing clonal heterogeneity,” the team noted. “The reversibility of ePV, without altering DNA sequence or incurring mutation costs, serves as an additional way for individual bacterial strains to adapt to diverse stresses … Our results indicate that in the human gut, ePVs may help bacterial populations regain heterogeneity after bottlenecks encountered during colonization of a new host or severe perturbations due to antibiotic exposures.”

The discoveries have several important implications for human health. In the field of probiotics, it may be that bacteria in a probiotic capsule are not in the same functional state as those that successfully establish themselves in the gut—potentially explaining inconsistent results. “Ultimately, our goal is to design probiotics that are better equipped to establish themselves in the gut and to develop therapies that support beneficial microbes while limiting harmful ones,” Fang said.

For FMT-based treatments, differences in these epigenetic states between donors and recipients may influence how well microbiota transplants work. And when considering antibiotic recovery, some gut bacteria may survive antibiotic treatment not because they are genetically resistant, but because a subset of cells is already in a protective epigenetic state that allows rapid rebound after treatment ends.

The research team plans to study larger groups of patients over time, particularly during and after antibiotic treatment and FMT. They also aim to explore whether similar mechanisms exist in other gut bacteria and to investigate how these epigenetic switches might be harnessed. In the longer term, understanding and potentially controlling these reversible switches could lead to more effective microbiome-based therapies, the investigators suggest.

“These ePV-driven regulatory mechanisms open new opportunities for targeted epigenetic interventions to improve the desired functions of beneficial bacteria,” the scientists stated. “For example, by manipulating ePV, we may strategically boost the resilience and functional capabilities of beneficial bacteria, which might improve the success rates of probiotic engraftment and the efficacy of treatments for microbiota-associated conditions.”

Regeneron Pharmaceuticals will partner with Parabilis Medicines to discover and develop an initial five candidates encompassing a new form of antibody-drug conjugates aimed at challenging and historically undruggable targets, through a strategic research collaboration that could generate up to $2.3 billion-plus for the Cambridge, MA, biotech.

Regeneron will marry its antibody capabilities with Parabilis’ stabilized helical peptide or Helicon™ platform, to develop both Antibody-Helicon™ Conjugates (AHCs) as well as stand-alone therapies based on Helicons—stabilized, cell-penetrant alpha-helical peptides designed to engage intracellular protein targets, including flat surfaces that are not well suited to traditional small molecule binding.

While ADCs traditionally use antibodies to selectively deliver drug payloads into target cells to induce their death from within, the AHCs envisioned by Regeneron and Parabilis would combine antibody-targeted cell access with Helicon payloads designed to selectively modulate specific intracellular proteins, including some long-undruggable proteins.

“In addition to the potential of Helicons to address previously undruggable targets, the collaboration’s intent to couple Helicons to our VelocImmune® derived-antibodies so as to precisely deliver them to cells of interest represents an exciting new approach with the potential to create an entirely new therapeutic class that can span multiple therapeutic areas,” George D. Yancopoulos, MD, PhD, Regeneron’s board co-chair, president, and CSO, said in a statement.

Regeneron has agreed to pay Parabilis $125 million, consisting of a $450 million upfront payment and commitment to invest $75 million in Parabilis’ next equity financing, subject to specified conditions. Regeneron also agreed to pay Parabilis payments tied to achieving development, regulatory, and commercial milestones, as well as tiered royalties up to the low double-digits on future net sales of any approved medicines resulting from the collaboration.

Five initial targets

With five initial targets, the collaboration agreement could generate up to approximately $2.2 billion in total milestone payments to Parabilis.

Under the terms of the agreement, additional targets may be pursued upon additional option payments from Regeneron.

Regeneron shares fell nearly 10% Monday, to $629.68, from Friday’s close of $698.25, and plateaued on Tuesday, inching up 0.1% to $630.30. The Monday drop reflected not the Parabilis deal but a clinical setback: Regeneron on Friday evening acknowledged the failure of a Phase III trial (NCT05352672) assessing two dose levels of the lymphocyte-activation gene-3 (LAG-3) inhibitor fianlimab in combination with a PD-1 inhibitor, Regeneron’s marketed drug Libtayo® (cemiplimab), as a first-line treatment for patients with previously-untreated, unresectable locally advanced or metastatic melanoma.

Fianlimab plus cemiplimab failed the trial by not reaching statistical significance for the primary endpoint of improvement in progression-free survival (PFS) compared to monotherapy with another PD-1 inhibitor, Merck & Co.’s Keytruda® (pembrolizumab), the multi-indication cancer immunotherapy, Regeneron said, in an announcement released more than four hours after the close of financial markets.

Parabilis, a privately held company which rebranded from FogPharma in 2024, rang in 2026 by announcing the closing of a $305 million Series F financing on January 8, with proceeds intended to support continued clinical development of its lead helicon peptide candidate zolucatetide (formerly FOG-001)—a first and only direct inhibitor of the elusive β-catenin:TCF interaction, according to the company—including progression toward a registrational trial in desmoid tumors and continued evaluation across genetically simple and more complex tumor types.

Positive preliminary data

In March, Parabilis presented preliminary clinical data at the 11th Biennial Meeting of the International Society for Gastrointestinal Hereditary Tumors (InSiGHT) showing significant improvement in duodenal polyposis at 60 weeks in a patient with familial adenomatous polyposis (FAP) treated with zolucatetide in the company’s ongoing Phase I/II trial (NCT05919264).

The patient showed a 52.2% reduction in desmoid tumor diameter, as well as “substantial” reductions in polyp number and size compared with a pre-treatment evaluation nearly two years prior, consistent with downstaging from Spigelman stage II to stage I.

The financing, Parabilis added, will also support advancement of its targeted discovery pipeline, including its prostate cancer franchise, and additional efforts to leverage the company’s Helicon platform to unlock long-undruggable disease targets.

In addition to zolucatetide, Parabilis’ pipeline includes:

• Two prostate cancer-fighting discovery phase programs, an ERG degrader Helicon program, and an androgen receptor degrader
• A beta-catenin degrader Helicon program targeting mutations in the Wnt/β-catenin pathway, linked to 80–90% of cases of colorectal cancer, that is also in discovery phase
• A Helicon-enabled alpha radioligand therapies (HEARTs) program against multiple cancer targets, a program partnered with ARTBIO, in hit identification phase.

“Through our own pipeline, we have demonstrated the potential of Helicon peptides to directly inhibit or degrade several disease-driving proteins in oncology that have long been considered out of reach,” stated Mathai Mammen, MD, PhD, Parabilis’ chairman, CEO, and president. “We are thrilled to enter into a collaboration with Regeneron that builds on this foundation, combining the intracellular access and binding capabilities of our Helicons against challenging targets with antibodies from Regeneron.”

Analysts are extremely encouraged by Phase 2 trial results for Relay Therapeutics’ PI3KA inhibitor in treating vascular malformations (VM), prompting the biotech to eye a potential path to accelerated approval.

Relay’s investigational PI3KA inhibitor has elicited a 60% response rate in patients with vascular malformations, toppling Novartis’ 11% overall response rate seen in a failed Phase 2 study of Vijoice. The biotech’s execs are now looking to the FDA’s accelerated approval pathway for the oral PI3KA inhibitor, called zovegalisib, pending additional data and feedback from regulators.

The early-stage data include adults and children older than 12 years with vascular anomalies—an umbrella term for rare disorders marked by abnormal development of blood vessels, lymphatic vessels and nearby tissues. As of April 15, 32 patients were enrolled in the Phase 2 ReInspire trial, of which 22 patients had PIK3Ca-related overgrowth spectrum (PROS)—disorders caused by mutations in the PI3Ka gene.

Of 20 evaluable patients, 12—or 60%—achieved a volumetric response at 12 weeks, according to data set for presentation Wednesday at the International Society for the Study of Vascular Anomalies World Congress 2026. The overall response rate (ORR) doubles Leerink Partners’ “prior bar for success” of 20%–25% ORR and is higher than the 11% ORR seen at week 16 for Novartis’ oral PI3K inhibitor Vijoice in a failed PROS study.

After Relay’s data cutoff of April 15, one additional patient had an unconfirmed response, resulting in a 65% (13/20) ORR, according to the Cambridge, Massachusetts–based biotech.

The data show “the full potential of what a mutant selective inhibitor can do in these vascular anomaly patients,” Relay CEO Sanjiv Patel said on a Tuesday conference call. “[We] believe this leaves very little room for improvement of our volumetric response rate for anyone that will come behind us.”

At 12 weeks, interim investigator-measured impressions of change showed 89% of patients experiencing clinical improvement, while patient reports for the same metric were 79%. Pain scores, as measured by investigators, demonstrated clinical improvement for 71% of symptoms.

“Given these superlative results, we think it is possible RLAY shares could exceed our anticipated >10% move as some investors may adopt VM as the main value driver,” Leerink said.

Since market open, the biotech’s stock has risen 9% to $13.29 per share.

The trial is testing doses of 100 mg, 300 mg and 400 mg twice daily. “We believe there is no further efficacy left on the table,” Patel said about the 300-mg dosing regimen. “As you go above that, you’re just seeing greater tolerability challenges, and so we don’t think there’s any room for us to go higher than 300.”

The rates of treatment-related adverse events (TRAEs) among 22 patients were “proportional to dose level,” with no dose discontinuations, according to Relay. Two patients (9%) experienced a grade 3 or higher TRAE.

Zovegalisib wasn’t tied to rashes or stomatitis of any grade, and no cases of grade 3 or higher hyperglycemia or diarrhea were reported, though the biotech did not disclose all the data for adverse events.

Overall, zovegalisib’s tolerability profile was generally “as expected and consistent with mutant-selective PI3Kα inhibition,” according to Relay. The rates of key adverse events such as hyperglycemia, stomatitis and rash were lower than or similar to Vijoice, according to Leerink.

Based on the newest findings, Relay is opening multiple expansion cohorts at 400 mg once a day and 300 mg twice daily in patients 12 years and older, with a dose-finding trial for patients aged six to 11 years ongoing. Zovegalisib is also in later-stage testing for multiple metastatic breast cancers.