The Massachusetts biotech will focus its efforts and resources into cemsidomide, an oral drug candidate being trialed for multiple myeloma and non-Hodgkin lymphoma. C4 Therapeutics will no longer pour money into its investigational BRAF inhibitor CFT1946, in the name of “strategic capital allocation,” the biotech announced Wednesday.
Instead, C4 will focus its efforts and resources on its multiple myeloma drug candidate cemsidomide, while looking for development partners that can “advance the BRAF program given the high unmet need and strong degrader rationale for treating BRAF V600 mutant solid tumors.”
Before being put on the backburner, CFT1946 had a Phase I readout last September, which demonstrated that the drug candidate had an encouraging pharmacokinetic and safety profile, according to the company.
These early results underscored the potential of CFT1946 to “disrupt the current treatment landscape” in these specific solid tumors, CEO Andrew Hirsch said at the time. BRAF is a signaling protein that frequently carries a V600 mutation in a variety of cancer types.
Data from a Phase I dose-escalation study of CFT1946 in patients with melanoma or colorectal cancer will be presented at an upcoming scientific congress, according to C4’s press announcement on Wednesday.
C4 announced its decision to put CFT1946 on ice alongside its first-quarter earnings report. In the first three months of 2025, the biotech recorded a net loss of $26.3 million, a slight improvement from its $28.4 million deficit during the same period last year. By the end of Q1, C4 had $234.7 million in cash, cash equivalents and marketable securities, enough to keep it afloat into 2027.
The Massachusetts-based biotech will now focus its efforts and resources on cemsidomide, an experimental oral degrader of IKZF1/3 transcription factors being trialed for multiple myeloma. According to C4, Phase I data for the drug candidate suggest a “compelling” response profile for cemsidomide in this indication, hitting an overall response rate of 50% as of an April 30 data cutoff.
C4 plans to wrap up the Phase I dose-escalation trial for cemsidomide and present its data by the third quarter.
Aside from multiple myeloma, C4 is also studying cemsidomide in non-Hodgkin’s lymphoma, for which it is also conducting Phase I dose-escalation analyses. The biotech is building up to a readout in this indication by year-end. C4 is awaiting certain “regulatory feedback” regarding cemsidomide’s registrational development, which it expects to receive by mid-year.
CRISPR Therapeutics’ partner Vertex reported that more than 65 treatment centers have been activated for the gene therapy Casgevy. While Vertex handles the market, CRISPR has been focused on its clinical program.
The outlook for CRISPR Therapeutics’ approved gene therapy Casgevy is starting to look up, with more treatment centers added over the past quarter. The positive trend comes just as the gene editing biotech reported that its cholesterol-lowering gene therapy dropped lipoprotein and triglycerides in a Phase I trial, showcasing the potential of gene therapy if the space can overcome its commercial hurdles.
CRISPR’s partner Vertex reported earlier this week that more than 65 treatment centers have been activated for Casgevy, which is approved for sickle cell disease and beta-thalassemia. The revelation provided a glimmer of hope for the gene therapy space, which has been battered by bad news.
Vertex reported revenue of $14.2 million for Casgevy in the first quarter, up a modest but encouraging 4%, according to William Blair analysts. This growth signals that “the ramp in patient starts is beginning to convert to a ramp in cell infusions,” the group wrote in a note to investors Wednesday morning.
In September 2024, patients finally started to receive infusions of Casgevy, 10 months after its December 2023 approval. It’s been a slow build for a modality that could have profound impacts on the lives of patients. The treatments have struggled to gain market share; they are expensive and challenging for patients to undergo. The companies involved have also had to build out a network of treatment centers capable of supporting patients through the process.
As CRISPR and Vertex have charged ahead, rival bluebird bio has fallen behind. Once a promising gene therapy company, bluebird sold itself to private equity earlier this year for a mere $30 million after failing to reach profitability in time to make up a looming cash gap.
But CRISPR has the backing of a much larger pharma company in Vertex, which has been leading the marketing efforts. Vertex has set a goal of activating 75 treatment centers globally, and has hit 65 already, Chief Operating Officer Stuart Arbuckle explained on Vertex’s first quarter earnings report Monday.
“Casgevy truly does have the potential to be a multibillion-dollar product for Vertex,” Arbuckle said.
About 90 patients have undergone the initial cell collection process, according to Arbuckle, and more than twice that number have been referred to begin treatment. A total of eight patients have completed treatment.
“It’s been inspiring to hear that Casgevy patients now feel able to live their lives in ways they never have before,” Arbuckle said. “Whether that means having the energy to play with their kids, taking up snowboarding without fear that the cold might bring on a pain crisis or investing in their education and careers given expectations now for a longer and healthier life. It is a privilege to be part of their journey.”
Laser-Focused
While Vertex handles the market, CRISPR has been cleared to focus on its clinical program, such as the in vivo liver editing program CTX310. On Tuesday, the company reported a small batch of data from just 10 patients with elevated lipoprotein (LDL) and triglyceride (TG) levels in a first-in-human trial of the gene therapy. A single dose of the treatment decreased expression of the ANGPTL3 gene, which is involved in the regulation of LDL and TG levels. Both LDL and TG decreased as well.
One patient with severe hypertriglyceridemia had an 82% reduction in TG. Another with heterozygous familial hypercholesterolemia had an 81% reduction in LDL-C, a measure of the cholesterol carried by LDL particles.
William Blair said the data “looks competitive” with LDL-C reductions seen with Arrowhead Therapeutics ARO-ANG3 and Regeneron’s approved therapy Evkeeza.
CTX310 was well tolerated and there were no severe adverse events reported. CRISPR also noted that liver enzymes were not elevated at any dose level.
CRISPR heralded the results as a “significant milestone” for its proprietary lipid nanoparticle (LNP) delivery technology for gene editing in the liver. More data from the Phase I trial will be presented at a medical meeting later this year. CRISPR is also developing CTX320 for cardiovascular disease, with a Phase I readout expected in the second quarter.
“We also think the safety profile of CTX310 de-risks the upcoming readout from CTX320, and we highlight that CRISPR is the only company with an in vivo gene-editing candidate targeting Lp(a) in the clinic,” William Blair said.
The company is also working on two preclinical programs, CTX340 for refractory hypertension and CTX450 for acute hepatic porphyrias. In oncology, CRISPR will have a readout for a Phase I trial of CTX131 in solid tumors and blood cancers sometime this year. An update for the regenerative medicine diabetes treatment CTX211 is also expected before the end of 2025.
“We view CRISPR as having a catalyst-rich 12-month period ahead as it advances candidates across its ex vivo and in vivo platforms through the clinic,” William Blair wrote.
Summary: A new study shows that improving emotional processing can significantly reduce chronic pain and improve quality of life. Researchers developed Pain and Emotion Therapy, an online intervention teaching emotional regulation, which led to notable pain reduction in participants.
Those who received the therapy reported lower pain intensity, better emotional regulation, and improved daily functioning up to six months later. The findings highlight emotional dysregulation as a crucial — and previously under-addressed — factor in chronic pain and suggest accessible, holistic solutions may transform future treatments.
Key Facts:
Emotion-Focused Therapy Works: Targeting emotional regulation led to a ~10-point reduction in pain intensity.
Long-Lasting Benefits: Improvements lasted up to six months, affecting pain, mood, and sleep.
Accessible and Scalable: Delivered online, the therapy reached patients across Australia, including remote areas.
Source: University of New South Wales
A new study led by UNSW Sydney and Neuroscience Research Australia (NeuRA) shows that targeting emotional processing is key to treating and managing chronic pain.
The study is based on a randomised controlled trial led by Professor Sylvia Gustin and Dr Nell Norman-Nott, both from UNSW and NeuRA.
Along with a team at NeuRA’s Centre for Pain IMPACT, they published their results today in JAMA Network Open.
The trial showed that enhancing the brain’s capacity for emotional processing through therapeutic intervention is an effective approach to managing chronic pain.
“By changing how we manage emotions, it is possible to change the experience of pain itself,” Prof. Gustin says.
“This is not just a temporary relief but a potential long-term improvement in quality of life for those affected by chronic pain.”
Prof. Gustin and Dr Norman-Nott developed Pain and Emotion Therapy — a novel and emerging eHealth intervention.
The therapy aims to retrain the brain to more easily process emotions by improving an individual’s ability to deescalate negative emotions and enhance positive ones.
The trial took place from March 2023 to September 2024 and focused on the experiences of 89 people with chronic pain.
The authors say the results could lead to new ways of treating chronic pain, emphasising the profound impact of emotional health on physical wellbeing.
The online therapy, made available through the trial, is the first of its kind, delivered through eight group-based therapist-guided sessions by video conference across Australia.
Participants also used an app and handbook for self-learning. The control group continued their usual treatment.
Prof. Gustin says those who received the new treatment reported better emotional regulation as well as pain reduction equal to a 10-point decrease on a 100-point scale for pain intensity within a six-month follow up.
“This shows not only a clinical improvement, but one that makes a noticeable difference in the daily lives of the people affected,” she says.
Understanding chronic pain
Chronic pain, defined as pain lasting longer than three months, affects around 30% of people globally. The economic costs are estimated to be higher than that of heart disease, cancer and diabetes combined.
Declining mental health is also widespread, with up to 80% of people with chronic pain experiencing depression and anxiety. In addition, suicide rates are two to three times higher than those of the general population.
“A key factor in disease progression is the inability to regulate negative emotions,” Prof. Gustin says.
“This is disrupted by the impact of persistent pain on the brain’s emotional circuitry. The resulting emotion dysregulation is an ill-understood and undertreated aspect of chronic pain, which we addressed in this trial.”
Study participant Jabez Allies has had chronic back pain for 10 years. She says chronic pain affects her emotions.
“It makes me feel more worried, moody and frustrated, which in turn affects my pain. The more negative emotions I have, the worse my pain is, and vice versa,” she says.
Prof. Gustin says this cycle of worsening pain and increasing negative emotions is a common presentation.
“It shows us that chronic pain really does have a considerable effect on how people feel and the level of pain they experience.”
A boost to traditional treatments
Dr Norman Nott says that in the past 50–60 years, the model of chronic pain has shifted focus.
“We’ve gone from purely medical and biological approaches to a more holistic treatment model that includes addressing social and psychological experiences,” Dr Norman Nott says.
She says while prescription and non-prescription pain medications continue to play an important role in treatment, they have limitations.
“I’m thinking particularly of side effects and diminishing efficacy over time. Opioids, specifically, present considerable issues with dependency and declining effectiveness.”
She says, “though psychological therapies come with few side effects, we know there are still improvements needed, particularly to address the key mental health concerns of people with chronic pain, such as identifying and expressing emotions, and calming down emotional reactiveness.
“The focus on training for emotional regulation appears to be the missing piece of the jigsaw puzzle of chronic pain treatment.
“This is why we created this therapy – to focus on emotion processing by improving how people manage their emotions.”
Richard Beaumont is a participant who has had cancer pain and chronic lower back pain for 11 years. He says he frequently gets pain that reaches an eight or nine out of 10.
“After receiving Pain and Emotion Therapy I can bring this right down to a four or five just by calming the farm,” he says.
Targeting the emotional brain
“Previous research shows us that the brain can be trained to identify negative emotions and regulate them,” Prof. Gustin says.
“With this trial we can now see that engaging emotion regulation skills can reduce the intensity of pain and improve several other factors such as depression, anxiety and sleep problems.”
Dr Norman-Nott says this new therapy works by teaching participants that we need emotions in our lives.
“Often when we live with chronic pain for many years, negative emotions get pushed down and positive emotions become harder to identify,” Dr Norman-Nott says.
“We focus on helping to identify and bring up those negative emotions so that they can be acknowledged and resolved – while also realising the potential positive aspects of life and setting goals for the future.”
Accessible treatment for all
The accessibility of psychological treatment for chronic pain is a key point of governmental concern.
The progression and management of the disease are further aggravated by long wait times and limited healthcare services outside of capital cities.
“Our online treatment delivery reduced barriers by making it accessible to those who struggle with mobility, social anxiety, or physical exhaustion from travelling to in-person appointments,” Dr Norman-Nott says.
“It enabled them to participate from every state in Australia, including many from remote and regional locations.
“Participants attended the online sessions from their homes, or wherever it was comfortable for them, so they could train their emotion regulation skills when it suited them via the customised app and workbook.”
The next step for rolling out Pain and Emotion Therapy is a larger clinical trial supported by the Medical Research Future Fund, due to start in 2026.
The researchers are now calling for participants to register their interest in the trial.
“The results we’ve seen so far are a big improvement in our understanding of chronic pain, showing how important it is to treat both the body and emotions together,” says Prof. Gustin.
A novel health-assessment tool uses eight metrics derived from a person’s physical exam and routine lab tests to characterize biological age. It may be able to predict a person’s risk of disability and death better than current health predictors.
University of Washington School of Medicine researchers describe their method in a May 5 Nature Communications paper.
The method, called the Health Octo Tool, might make it possible to identify new factors that affect aging, and to design interventions that prolong life, said the report’s first author, Dr. Shabnam Salimi. She is a physician-scientist and acting instructor in the Department of Anesthesiology & Pain Medicine. She is also an investigator at the UW Medicine Healthy Aging & Longevity Research Institute
Current health-assessment methods focus on the effects of individual diseases but fail to consider the interactions among diseases and the impact of minor disorders on overall health, Salimi said.
“An aging-based framework offers a new path to discover biomarkers and therapeutics that target organ-specific or whole-body aging, rather than individual diseases,” Salimi said.
The approach is based on a concept of aging called “health entropy.” The term applies to the amount of molecular and cellular damage the body has accumulated over time, and how that damage has affected organ and system function. Thus, health entropy could serve as a measure of an individual’s overall physical well-being and be translated to describe a person’s pace of aging.
The researchers analyzed data from the Baltimore Longitudinal Study on Aging, one of the longest-running studies of adults as they grow older. The data included participants’ medical history and the results of their physical exams and medical tests. To validate their new approach, researchers then analyzed the results of two other large studies that traced the health of more than 45,000 adults.
The researchers began by establishing what they called a Body Organ Disease Number. This was based on the number of organ systems, such as cardiovascular, respiratory and central nervous systems, that were affected by disease and whether the individual had experienced cancer or a stroke. This score could range from 1 to 14.
“Our findings demonstrated that organ systems age at different rates, prompting us to develop a Bodily System-Specific Age metric to reflect the aging rate of each organ system and the Bodily-Specific Clock to represent each organ system’s intrinsic biological age,” Salimi said. “Extending this concept to the whole body, we define the Body Clock as a composite measure of overall intrinsic age and Body Age as the corresponding rate of aging.”
Because not all people of the same biological age experience the same functional decline, the researchers also developed what they called a Speed-Body Clock and Speed-Body Age to describe how biological age affects walking speed, a common measure of function in older people. They also created a Disability-Body Clock and Disability Body Age, to gauge how intrinsic aging affects the risk of cognitive and physical disability.
“Collectively, these eight metrics—Body Clock, Body Age, system-specific clocks and rates, Speed- and Disability-based clocks—offer a way to view an individual’s aging process with information gathered from their medical history, physical exam and test results alone,” Salimi said.
Of particular interest was the finding that some conditions that might be considered minor problems, such as untreated hypertension early in life, can have a major effect on aging later, indicating that early treatment of these conditions might have a big impact, Salimi said.
The research team is now developing a digital application that will allow individuals, with their health care providers, to determine their body and organ’s biological ages and track their rate of aging and assess the effect of lifestyle changes and treatments.
“Whether someone is adopting a new diet, exercise routine or taking longevity-targeting drugs, they will be able to visualize how their body—and each organ system—is responding,” she said.
Daniel Raftery, professor of anesthesiology and pain medicine at the UW School of Medicine and director of the Northwest Metabolomics Research Center, and Dr. Luigi Ferrucci, scientific director of the National Institute on Aging, are the senior co-authors of the paper.
Paris-based Astraveus formed a strategic partnership with The Netherlands Center for the Clinical Advancement of Stem Cell and Gene Therapies (NecstGen) to evaluate The Lakhesys Benchtop Cell Factory™ for the manufacturing of CAR-T therapies.
NecstGen will use Astraveus’ Lakhesys product at its facility in Leiden to determine its potential to reduce costs and increase efficiency in CAR-T manufacturing compared to current industry benchmarks. Additionally, NecstGen will produce Lentiviral vectors for Astraveus’ internal research and development needs.
Officials at Astraveus said its scientists recently demonstrated the potential of the Lakhesys with the first, end-to-end production of CAR-T cells within a microfluidic benchtop system. The company is now starting external testing of its new manufacturing platform. Astraveus’ technology and its microfluidic approach possess the ability to simultaneously decrease manufacturing costs as well as increase process efficiency and throughput, according to Jérémie Laurent, PhD, CEO of Astraveus.
“This partnership, with a leading European center of excellence for cell and gene therapy, enables Astraveus to carry out external system demonstrations of our disruptive technology in a highly collaborative and transparent manner,” said Laurent.
“Astraveus’ novel approach to the manufacturing of CAR-T cells represents a breakthrough technology with the ability to transform the industry by enabling the faster and cheaper development of these cutting-edge treatments,” added Paul Bilars, CEO of NecstGen.
Located in a purpose-built GMP facility at the Leiden Bio Science Park, NecstGen, a non-profit CDMO, supports academic, small, and large industrial therapy developers to translate research and early-stage clinical programs into patient treatments.
Bristol Myers Squibb, Board Chair of BMS and CEO Christopher Boerner, PhD, have committed the pharma giant to investing $40 billion over the next five years toward U.S. research and development (R&D), technology, and manufacturing efforts.
“Through this investment plan, we will strengthen our presence across the country, ramp up radiopharmaceutical manufacturing, and invest in artificial intelligence and machine learning to help us significantly increase the pace of innovation,” Boerner stated in a commentary published in STAT News.
Boerner did not detail the projects that BMS plans to invest in, specify which ones would be new construction or renovation, or offer a projected number of jobs to be created.
Artificial intelligence (AI) investment has emerged as a BMS priority. Robert Plenge, MD, PhD, executive vice president, chief research officer, and head of research joining Greg Meyers, executive vice president and chief digital & technology officer, recently told GEN Edge the company’s approach to AI and successful applications.
“For more than 160 years, the majority of Bristol Myers Squibb’s employees, R&D investments, and manufacturing infrastructure have been based in the United States. And we have no plans for that to change.”
Boerner’s investment pledge makes BMS the latest biopharma giant to join a growing parade of drug and diagnostics developers that have announced more than $200 billion in new and renovated facilities. Primarily focused on manufacturing, some developers also work with R&D and other operations. The announcements have trickled out in recent months as President Donald Trump’s administration has pressed the industry to make more of its products in the U.S., in part by threatening to impose tariffs on pharma imports.
“In anticipation of potential tariffs, we continue to execute mitigation efforts. We have a broad global manufacturing network where we’re looking for opportunities to optimize with tariffs in mind,” Boerner told analysts April 24 on the company’s first quarter earnings call, adding: “We already have a significant presence in the U.S. and we’re continuing to invest.”
Domestic manufacturing order
Yesterday, Trump stepped up Washington’s full-court press on biopharma to promote more domestic manufacturing, by signing an executive order executive order directing FDA Commissioner Martin Makary, MD, to:
• Review existing regulations and guidance pertaining to domestic pharmaceutical manufacturing development.
• Take steps to eliminate any duplicative or unnecessary requirements in such regulations and guidance.
• Maximize the timeliness and predictability of agency review.
• Streamline and accelerate the development of domestic pharmaceutical manufacturing.
“The FDA Commissioner’s review shall encompass all regulations and guidance that apply to the inspection and approval of new and expanded manufacturing capacity, emerging technologies that enable the manufacturing of pharmaceutical products, active pharmaceutical ingredients, key starting materials, and associated raw materials in the United States,” according to Trump’s order.
That order also directed Environmental Protection Agency (EPA) Administrator Lee Zeldin to update regulations and guidance applying to U.S. inspection and approval of new and expanded manufacturing capacity of pharmaceutical products, active pharmaceutical ingredients, key starting materials, and associated raw materials.
Warning on pricing, tariffs
Boerner warned against policies that would cut U.S. spending toward drug production, or set prices along the lines of European countries, which he asserted “has limited the availability of new medicines and significantly slowed their adoption.” Trump’s administration is reported to be considering adopting for Medicaid-paid drugs a “most-favored nation” (MFN) pricing approach, which bases the prices of U.S. treatments on the lowest prices paid in comparable countries.
But the BMS CEO aligned with the president on a key policy priority, urging Congress to extend the series of tax cuts that Trump’s first administration enacted in 2017 through the Tax Cuts and Jobs Act, set to expire at the end of this year.
“This presidential administration and some members of Congress have championed policies that will strengthen American innovation and competitiveness. Bolstering U.S. manufacturing enables greater control over highly complex supply chains and bring manufacturing closer to where the majority of R&D is taking place,” Boerner wrote. “Extending supportive tax policies from President Trump’s first term would further enhance U.S.-based research spending.”
The largest of the biopharma commitments to U.S. manufacturing and R&D has been made by Johnson & Johnson, which has promised to invest $55 billion over four years. Other biopharma commitments have been made by Roche ($50 billion over five years), Eli Lilly ($27 billion, on top of $23 billion spent since 2020), Novartis ($23 billion over five years), AstraZeneca ($3.5 billion by the end of 2026), Amgen ($1 billion second manufacturing plant in Holly Springs, NC, $900 million expansion in New Albany, OH), and Thermo Fisher Scientific ($2 billion over four years).
Merck & Co. has committed $9 billion, including a $1 billion biologics center of excellence in Wilmington, DE, that has broken ground and a $1 billion vaccine manufacturing facility that has opened in Durham, NC—in addition to $12 billion invested in U.S. manufacturing and R&D projects since 2018.
Regeneron Pharmaceuticals last month joined with contract development and manufacturing organization (CDMO) giant Fujifilm Diosynth Biotechnologies to announce a 10-year, $3 billion-plus manufacturing supply agreement designed to provide U.S.-based production of biologics.
Layoffs in Lawrence Township
Boerner disclosed BMS’ U.S. investment plans the same day New Jersey news outlets disclosed BMS’ planned elimination of 516 jobs in Lawrence Township, NJ, based on a series of Worker Adjustment and Retraining Notification (WARN) Act notices made public by the state’s Department of Labor & Workforce Development. The 516 jobs will be eliminated in 14 groups starting Friday and running through March 27, 2026.
The 516 jobs are among three rounds of job cuts at the facility totaling 806 positions set to be eliminated this year. BMS began eliminating the first set of 67 jobs April 24, to end December 11. A second round of 223 jobs will disappear between May 22 and August 1.
The state listing of notices did not specify the types of jobs being eliminated or the nature of those jobs, or whether jobs would be cut at one or both of BMS’ campuses in Lawrence Township:
• Lawrenceville—BMS now houses its R&D headquarters within a 276-acre campus on Route 206 consisting of 13 connected buildings totaling 1.5 million square feet. R&D researchers based their focus on discovering and developing therapies in oncology, immunology, and cardiovascular diseases, three of the company’s five R&D areas of focus (the others are hematology and neuroscience).
• Princeton Pike—Employees from BMS’ commercial teams, their commercialization and late-stage development partners from its R&D and Global Manufacturing & Supply operations, as well as their enabling function support teams are based within a 650,000-square foot facility that opened in 2016.
The New Jersey job cuts come at a time when BMS is carrying out two cost-cutting initiatives—an initial plan to eliminate $1.5 billion in expenses by the end of this year, plus a newer effort to slice $2 billion in company costs by the end of 2027, announced by the company on February 6 when it reported fourth-quarter and full-year 2024 results.
BMS has blamed the cost-cutting initiatives on its need to recoup losses expected as some of its “blockbuster” drugs that have long generated more than $1 billion in sales lose patent exclusivity. Two such drugs will lose U.S. patent protection in 2028—cancer immunotherapy Opdivo® (nivolumab), which generated $9.304 billion in 2024 product revenues (up 3% from 2023); and Eliquis® (apixaban), a blood thinner that racked up $13.333 billion in 2024 (up 9% year over year).
Biopharma venture capital fundraising declined from $8.1 billion in the first quarter of 2024 to $6.5 billion in the first three months of this year, headlined by a clutch of massive funding rounds. Venture capital financing declined 20% year over year in the first quarter of 2025, with a few massive raises holding things together for the industry.
A new report from GlobalData on VC trends in the sector outlined the steep decline in fundraisings as investors continue to avoid risk. Financings declined from $8.1 billion in the first quarter of 2024 to $6.5 billion in the first three months of this year. This returns VC spending to the two-year downturn seen post-pandemic in 2022 and 2023, after a brief uptick in 2024, GlobalData noted.
There were 162 total VC investments in the pharma sector in the first quarter, GlobalData said. These raises tipped toward later-stage firms with clinical data.
“The higher deal values for late-stage firms underscores a distinct realignment of investor risk appetite—a trend observed since 2024,” Alison Labya, business fundamentals pharma analyst at GlobalData, said in a statement. “Amid the ongoing macroeconomic uncertainty, venture capitalists are favoring opportunities with clearer routes to near-term revenue and market access over longer-horizon development risks.”
Phase III companies had the highest median deal value for the first quarter with $62.5 million, a 39% increase compared to $45 million for the entirety of 2021. In 2024, though, these late-stage deals had a median of about $100 million.
This year’s first quarter numbers are influenced by some massive standout fundraises. Another report from J.P. Morgan found that 19 venture capital rounds raised $100 million or more in the period. The firm credited Isomorphic Labs, the Google AI drug discovery venture, with the largest fundraising of the quarter. Isomorphic’s $600 million fundraising was announced at the end of March. The company has boldly set out to “solve all diseases.”
Unsurprisingly, an obesity biotech had another of the largest VC rounds last quarter. Verdiva Bio debuted in early January with a massive $410 million in funds to start with. The company plans to develop next-generation oral and injectable obesity treatments, including an oral GLP-1 receptor antagonist that is in preparations for Phase II. Verdiva also has two earlier stage amylin programs.
VC darling Eikon Therapeutics, headed by a class of former Merck alums, was also among the top raise-earners, announcing a $350.7 million series D in February. The cash was to be spent on pushing lead candidate EIK1001 into a Phase III clinical trial. There could be more to come, too. Eikon said the February announcement was just the “initial closing.”
Eikon broke cover in 2021 with a $148 million series A to develop live-cell super-resolution microscopy for drug discovery. The company, which made BioSpace’s NextGen list of top startups to watch in 2022, has now raised $1.1 billion in total, some of which was used to purchase a clutch of assets to accelerate from discovery to the clinic.
Newer to the scene is cardiovascular-focused Kardigan, which launched in early January with a $300 million series A to find new treatments via a research platform and through acquisitions. The company is lead by former executives from MyoKardia, the biotech that was bought by Bristol Myers Squibb for $13.1 billion in October 2020.
Aviceda Therapeutics collected the fifth largest venture capital round in the first quarter, raising a series C worth $207.5 million. The company is developing immunomodulators for inflammatory diseases. The fundraise will be used to move lead asset AVD-104 into clinical trials for geographic atrophy.
A new executive order from President Donald Trump aims to cut down the 5-to-10-year timeline to build new facilities while stepping up the rigor of inspections on foreign plants.
President Donald Trump has ordered the FDA to cut down the time it takes to approve pharmaceutical manufacturing plants in the U.S. The new executive order also sets the groundwork for the FDA to implement surprise inspections on foreign plants, instead of planned visits as is the current process.
“We have had this crazy system in the United States where American pharma manufacturers in the United States are put through the wringer with inspections, and the foreign sites get off easy with scheduled visits,” FDA Commissioner Marty Makary said from the White House Monday afternoon. “A scheduled visit is no inspection, so we are, at the FDA, delivering on this promise in the President’s executive order and switching from announced to surprise inspections overseas.”
The order will also cut down on the time inspectors spend in the countries, allowing them to “get in and out,” conducting more inspections with the same amount of resources, Makary said.
The action on pharmaceutical manufacturing is the latest in Trump’s salvo to onshore the industry’s manufacturing. The executive order, issued Monday afternoon, aims to cut down the 5-to-10-year timeline to build new facilities. This lengthy process is “unacceptable from a national security standpoint,” according to the order.
“We don’t want to be buying our pharmaceuticals from other countries because if we’re in a war, we’re in a problem, we want to be able to make our own,” the president said in a statement accompanying the executive order.
At the Monday press briefing, Trump also foreshadowed more to come on drug pricing and tariffs, promising an announcement next week on the cost of medicines. When asked by a reporter on the timeline for tariff policy on the pharmaceutical industry, he said he’d provide more information over the next two weeks.
“We’re being ripped off, as you know, very badly being ripped off compared to the rest of the world,” Trump said of drug prices.
Building a ‘Tariff Wall’
Trump’s executive order came as Bristol Myers Squibb added itself to the list of Big Pharmas that have announced massive manufacturing spending on U.S. facilities. On Monday, CEO Chris Boerner said the company would spend $40 billion over the next five years, following similarly commitments from Eli Lilly, Novartis, Johnson & Johnson, Merck and more, all seemingly hoping to ease the administration’s concerns and avoid expensive tariffs on drug imports.
Pfizer CEO Albert Bourla acknowledged Trump’s “legitimate” concerns about national security during an earnings call last week. But he urged the president to move on from the tariffs and instead implement tax reform to encourage manufacturing to move to the U.S. His comments echoed those of J&J CEO Joaquin Duato and Amgen CFO Peter Griffith.
Despite the suggestion of tariffs to come, Jefferies analysts saw an inkling of good news in Trump’s latest posturing on the issue. The firm wrote Monday evening that the resulting policy “would not be as bad as expected.” Jefferies said that Trump has suggested he may allow 100% tax deductible expensing for four years as companies build U.S.-based plants, followed by what the president has called a “tariff wall.” Previously, rumors had swirled that this tax period would only be a year before the tariffs came down.
Trump’s drug pricing comments have also suggested that the feared revival of Most Favored Nations drug pricing may only apply to Medicaid drug pricing rather than cutting applicable patients, which would lessen the blow.
The House of Representatives, however, has been pushing for massive cuts to Medicaid, which Jefferies noted is at odds with what’s coming out of the White House. A recent House proposal called for $880 billion in cuts from Medicaid.
Mandate for Makary
The new executive order boosts fees for foreign plant inspections and requires the FDA to step up enforcement of active pharmaceutical ingredient source reporting.
Trump has also called on FDA commissioner Marty Makary to review existing regulations that relate to domestic manufacturing to eliminate any steps that may be slowing down the build out of manufacturing facilities. Makary should review all processes related to the inspection and approval of new and expanded facilities.
The order also calls for increased fees for foreign plant inspections and the implementation of surprise inspections on these ex-U.S. facilities. The order argues that facilities in the states face more robust inspections. It also calls for a public report of the number of foreign inspections the FDA performs, with detail on where they were conducted and on which manufacturer.
Trump’s order also called for coordination with the FDA to streamline environmental permits required to build out a pharmaceutical manufacturing facility.
Mammalian sperm are unusually picky. They prefer cooler environments, thriving below normal body temperature. Yet, they must navigate the female reproductive tract, which is warmer. So how do they survive and succeed?
New research from Washington University School of Medicine in St. Louis explains how. Sperm use the temperature difference as a signal.
When they enter the warmer female reproductive tract, they switch behavior. They move from calm, forward swimming to a vigorous, whip-like thrash. This change helps them pierce the egg for fertilization.
This discovery sheds light on male fertility. It also opens new directions for contraception.
Heat flips a sperm switch
All mammals carry a sperm-surface protein called CatSper. It regulates ion entry, powering the tail’s strong motions. Scientists found that temperatures above 38°C (100.4°F) activate this protein.
“That hyperactive state in sperm is key for successful fertilization, and no one knew exactly how temperature triggers it,” said Polina Lishko, PhD, professor of cell biology and physiology at WashU Medicine.
“Our work has identified a temperature-controlled switch in sperm that triggers these increased movements precisely when they are needed during fertilization.”
Before this study, CatSper was thought to respond only to pH and progesterone. But most mammalian sperm ignore progesterone. Temperature turns out to be the real switch.
This change explains why testicles hang outside the body. Evolution keeps them cool so sperm remain inactive until they reach warmer territory – then, they activate at just the right moment.
Mammals evolved to keep sperm cool
Humans aren’t the only species with clever cooling tricks. Dolphins pass blood through their dorsal fins to cool it before it reaches their testes. Elephants do the same through their ears. These adaptations protect the sperm’s sensitivity.
Birds, which lack CatSper, don’t need this. Their sperm do not rely on the same activation signal. This protein, and its temperature-based switch, is unique to mammals.
Using advanced tools, the researchers watched electric charges shift inside individual sperm. When exposed to higher temperatures, CatSper lit up. This marked the start of vigorous movement – just in time for fertilization.
Using heat to make sperm hyperactive
CatSper’s exclusive presence in sperm makes it an ideal drug target. Previous attempts to block it didn’t work well. But Lishko suggests a twist: instead of blocking it, activate it too early.
“Instead of creating inhibitors, it might be possible to activate CatSper with temperature thus, prematurely switching on this channel to drain the sperm of energy, so that by the time the sperm cell is ready to do its job and enter the egg cell, it is powerless,” said Lishko.
If successful, this method could prevent fertilization without affecting the rest of the body. It may also help men struggling with infertility by ensuring proper sperm activation.
Ovarian changes reduce fertility
While sperm need temperature to activate, the female reproductive system faces a different aging problem.
The researchers examined 62 human ovaries from donors aged 20 to 77. Using advanced gene-mapping tools, they found that different ovarian regions age at different rates.
The ovarian cortex, which houses immature eggs, showed signs of decline after age 40. The follicular niche – the support system for eggs – starts breaking down. In the medulla, immune activity ramps up by age 30. These changes reduce fertility well before menopause.
Egg support in aging ovaries
Granulosa and stromal cells showed the most dramatic aging. Fibroblasts, the builders of connective tissue, multiply in aging ovaries. They deposit fibrotic proteins that stiffen the ovarian tissue.
One key factor behind this fibrosis is reduced TGF-beta signaling. This pathway helps regulate repair and inflammation. Its loss leads to unchecked buildup of scar-like tissue in the ovarian cortex.
Over time, this damages the egg’s environment, even if some eggs remain. Fertility fades not just because of egg loss, but because the surrounding support system collapses.
Future fertility treatments
These studies together offer a broader view of fertility. In men, it’s about activation – timing sperm behavior using heat. In women, it’s about preservation – protecting the ovarian environment from early decline.
New therapies might target these weak points. In men, premature CatSper activation could offer safe birth control. In women, boosting TGF-beta or controlling fibrosis might preserve fertility longer.
Understanding both perspectives – activation and aging – could help design next-generation fertility treatments that support both partners in reproduction.
The study is published in the journal Nature Communications.
The benefits of avoiding shingles through vaccinations are piling up. New research out this week has found a link between getting vaccinated for shingles and a reduced risk of heart attacks and strokes.
Researchers from Kyung Hee University in South Korea led the study, published Monday in the European Heart Journal. They studied the medical records of over a million South Korean residents, finding that shingles-vaccinated people were noticeably less likely to develop cardiovascular disease than unvaccinated people. The findings are the latest to indicate that shingles is even worse for our health than currently thought.
“This suggests that the vaccine may provide not only protection against shingles itself but also potential benefits for heart health,” study researcher Sooji Lee told Gizmodo in an email.
Shingles is caused by the varicella zoster virus, the same germ that causes chickenpox in children. Though chickenpox is usually short-lasting, if unpleasant, the virus can survive the initial immune response and lie dormant in our bodies for decades. When our immune system gets weaker, usually due to age, the virus can reactivate and trigger a new infection that we call shingles.
This second bout is typically worse, causing symptoms like excruciating pain and rashes that last for several weeks. Sometimes, shingles can even leave behind lingering, potentially lifelong nerve pain.
As bad as shingles is, ongoing research suggests it may also increase the risk of future health problems. Multiple studies have linked shingles to a greater risk of Alzheimer’s disease and dementia, for instance—and conversely, a lower risk of dementia has been linked to shingles vaccination. Some studies have also suggested that shingles can cause heart complications after infection. But according to the researchers, there hasn’t been extensive research looking into whether vaccination can prevent these problems from arising.
In South Korea, healthcare is largely covered through a single-payer, publicly funded system. This system means that scientists can more easily study the health of South Korea’s population using de-identified (anonymous) data. The researchers cross-referenced different sources of data to track the shingles vaccination status and cardiovascular health of South Korean residents aged 50 and above starting in 2012, when the vaccine first became available in the country.
They ultimately found that shingles vaccination was associated with a 23% lower risk of any new cardiovascular condition, along with a 26% lower risk of major cardiovascular events (heart attacks and strokes) and a 26% lower risk of heart failure. The associated reduction in cardiovascular disease was strongest in the first two to three years following vaccination, but could still be seen up to eight years later. The protection from vaccination also appeared to be stronger in men, people in poorer pre-existing health, and people living in rural or low-income neighborhoods.
“Because our study was conducted in a large general population, these findings may be broadly applicable,” Lee said.
These sorts of studies are observational, meaning that they can’t definitively prove a causative link between two factors, only show a correlation (in this case, between shingles vaccination and reduced heart disease). But the authors note that shingles can cause inflammation, clots, and general blood vessel damage—all known risk factors for cardiovascular disease. They also speculate that the nerve damage caused by shingles could possibly disturb our heart rhythm, which can trigger problems like cardiac arrest.
Another consideration is that the researchers only studied the potential effects of an older shingles vaccine, Zostavax, one that uses a weakened version of the virus to generate immunity. That vaccine has largely been replaced by a different type of shingles vaccine named Shingrix that only uses a protein from the virus. This newer vaccine is more effective at preventing shingles, and some research has suggested that it might offer greater protection from dementia as well.
Lee says that her team is now planning to study whether Shingrix can potentially offer the same level of protection against cardiovascular disease as the older vaccine—or even better.
All that said, shingles can be extremely unpleasant, so getting vaccinated against it is already worthwhile. If we’re lucky, the vaccine might boost our brain and heart health, too.
