Tag: Appetite and ingestive regulation

Posted on
<![CDATA[Researchers at the ASCP Annual Meeting reported on how impaired brain insulin signaling may predict worsening depression severity and the links between metabolism and mood.]]>
Posted on

Triple Play: Lilly Acquires Three Developers of Infectious Disease Vaccines for Up-to-$3.8B

Eli Lilly has agreed to acquire three privately-held developers of vaccines for infectious diseases for a combined up to $3.83 billion cash, the companies said today, in deals intended to expand the acquisitive pharma giant’s R&D efforts into infectious disease—and which represent Lilly’s eighth, ninth, and 10th planned buyouts of smaller biotechs this year alone.

Lilly announced planned acquisitions of Vaccine Company for up to $1.55 billion, Curevo for up to $1.5 billion, and LimmaTech Biologics for up to $780 million. The planned triple play of buyouts, Lilly said, will enable it to apply differentiated technology platforms toward attacking infectious diseases, focusing on viral pathogens linked to long-term neurological and oncological risk, plus bacterial pathogens long considered difficult to prevent or treat.

“These acquisitions reflect a deliberate strategy to prevent disease at its source rather than treat its consequences,” Daniel M. Skovronsky, MD, PhD, chief scientific and product officer, and president, Lilly Research Laboratories, said in a statement.

“Decades of evidence now link common infections to diseases that potentially emerge years later, including neurological disease, cancer and infertility. And as antimicrobial resistance erodes our ability to treat bacterial infections, vaccines are increasingly the only path to prevention,” Skovronsky added. “Combining these companies’ platforms and teams with Lilly’s global scale positions us to change that trajectory.”

Investors appeared to support the triple play, sending Lilly shares up 1.36% to $1,079.19 as of 11:56 a.m. ET, from $1,065 at Friday’s close of trading.

Capitalizing on tirzepatide billions

The deal spree reflects Lilly’s desire to capitalize on the billions of dollars it is generating from sales of its obesity and diabetes drugs based on glucagon-like peptide 1 (GLP-1) receptor analysts alone or in tandem with a glucose-dependent insulinotropic polypeptide (GIP).

Those drugs account for 58% or $49.329 billion of the $84.978 billion in revenues reported by Lilly in 2025 and the first quarter of 2026. Lilly markets tirzepatide, a GLP-1/GIP dual agonist, in obesity as Zepbound® ($13.542 billion in 2025, $4.16 billion in first quarter 2026) and in diabetes as Mounjaro® ($22.965 billion, $8.662 billion in Q1 ‘26).

Lilly executives did not mention infectious diseases as a potential area of future growth during the company’s most recent earnings call last month with analysts following Q1 results, even as it cited three other therapeutic areas: I&I (immunology and inflammation), neuroscience, and oncology.

“We’re proud of what we’re doing in those three areas, and I think each of them has very significant unmet medical needs that we can scale into as our medicines are successful. We like what we got, and we like the direction we’re going. Of course, in each of those areas, we also see opportunities to get a lot bigger, and we’ve highlighted some of the themes already in those areas,” Skovronsky said on the April 30 call.

“Even without the obesity and metabolic business, Lilly would be the fastest or surely one of the fastest-growing pharmaceutical companies in the industry,” Skovronsky added.

Parade of purchases

Lilly’s long parade of purchases began January 7 when it inked a $1.2 billion acquisition of Ventyx Biosciences, an NLRP3-targeting oral drug developer focused on inflammatory diseases. A month earlier, Lilly announced plans to buy out circular RNA cell therapy developer Orna Therapeutics for up to $2.4 billion, targeting advancements in cell therapy. And in March, Lilly committed up to $7.8 billion to acquire Centessa Therapeutics, a developer of sleep disorder drugs.

Last month, Lilly agreed to acquire three cancer drug companies—in vivo chimeric antigen receptor T-cell (CAR T) developer Kelonia Therapeutics for up to $7 billion; JAK inhibitor developer Ajax Therapeutics for up to $2.3 billion; and next-generation dual-payload antibody-drug conjugate (ADC) developer CrossBridge Bio for up to $300 million.

Just last week on May 20, non-viral DNA delivery-focused drug developer Engage Biologics announced it had been acquired by Lilly for up to $202 million cash, including an upfront payment and payments upon achieving specified development milestones.

As for the latest planned acquisitions:

South San Francisco, CA-based Vaccine Company is developing in vivo nanoparticle (IVN) technologies designed to enable the antigen display known to elicit durable immune responses associated with virus-like particle vaccines, while avoiding the manufacturing burden of traditional VLP production. The company is advancing a preclinical pipeline spanning multiple viral pathogens; the lead program applies this technology to Epstein-Barr Virus (EBV) with a five-antigen Phase I-ready candidate.

Preventing mono and consequences

Lilly and Vaccine Company reason that a prophylactic vaccine could prevent not only acute infectious mononucleosis but also long-term neurological and oncological consequences that may follow infection, given what it said was growing evidence linking EBV to multiple sclerosis and several malignancies,

Under the acquisition deal, Lilly agreed to give Vaccine Company shareholders up to $1.55 billion, which would include an undisclosed upfront payment and additional payments tied to achieving specified clinical and commercial milestones.

LimmaTech Biologics, based near Zurich in Schlieren, Switzerland, is a developer of vaccines targeting bacterial pathogens for which rising antimicrobial resistance is steadily closing therapeutic options, including Staphylococcus aureus, Neisseria gonorrhoeae, and Chlamydia trachomatis. LimmaTech’s platform is designed to generate broad, durable immune responses against complex bacterial targets by targeting the toxins and superantigens that drive disease.

LimmaTech’s lead program, LTB-SA7, is in Phase I development as a vaccine against S. aureus, the leading cause of surgical-site infection. The company has also developed a preclinical pipeline of candidates targeting additional bacterial pathogens, including those that drive infertility and other long-term consequences of infection that fall disproportionately on women.

Lilly has agreed to acquire LimmaTech for up to $780 million, which will include an undisclosed upfront payment and additional potential payments also tied to achieving specified clinical and regulatory milestones.

Seeking greater tolerability

Bothell, WA-based Curevo has an infectious disease vaccine pipeline led by amezosvatein, an adjuvanted subunit vaccine being developed for the prevention of shingles in adults. Curevo acknowledges that the current standard of care for shingles prevention, GlaxoSmithKline (GSK)’s Shingrix® (Zoster Vaccine Recombinant, Adjuvanted) is effective, but says tolerability challenges can limit overall vaccination rates and contribute to second-dose hesitancy, leaving a meaningful portion of patients with reduced or no protection against shingles and its long-term consequences.

To prevent that problem, amezosvatein has been engineered with a next-generation synthetic adjuvant. In a Phase II trial head-to-head against Shingrix, amezosvatein matched immune response across all primary endpoints and reduced side effects such as activity-limiting fatigue, chills, and pain at the injection site by more than half. Lilly and Curevo reason that in light of growing evidence linking shingles to elevated risk of stroke and tying shingles vaccination to lower risk of dementia, a better-tolerated vaccine could reduce these long-term risks, thus expanding the reach of shingles prevention.

Lilly’s up to $1.5 billion deal price for Curevo includes another upfront payment and an additional payment hinging upon achievement of a certain milestone, all unspecified.

All three deals are subject to customary closing conditions, including expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976. Lilly said it will determine the accounting treatment of the transactions upon closing, in accordance with Generally Accepted Accounting Principles (GAAP). The transactions will be reflected in Lilly’s future financial results and financial guidance to investors.

That guidance was raised last month after Lilly reported stellar first quarter earnings tied to booming sale of its blockbuster tirzepatide-based drugs. Lilly raised its full-year 2026 revenue guidance to between $82 billion and $85 billion, and non-GAAP earnings per share (EPS) guidance to be in the range of $35.50 to $37.00.

In February, Lilly guided investors to between $80 billion and $83 billion in revenue, and non-GAAP EPS ranging from of $33.50 to $35.00.

The post Triple Play: Lilly Acquires Three Developers of Infectious Disease Vaccines for Up-to-$3.8B appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

STAT+: Eli Lilly to buy three small vaccine developers

Eli Lilly said Tuesday it would buy three early- and mid-stage vaccine developers, a boost for the field. 

The deals — which together could cost up to nearly $4 billion — are the latest acquisitions from Lilly, a company rich with cash from its booming GLP-1 business. In recent months, it’s picked up companies working on cancer, autoimmune diseases, and sleep disorders, all for under $10 billion each. 

The companies being bought are Curevo, LimmaTech Biologics, and Vaccine Company. 

Continue to STAT+ to read the full story…

Posted on

Craving fullness: a fullness-seeking phenotype that blurs the line between binge eating disorder and food addiction

Food addiction and binge eating disorder show striking clinical overlap that current diagnostic frameworks do not fully capture. In binge eating disorder samples, Yale Food Addiction Scale-defined food addiction has been reported in roughly half of participants. Higher symptom severity is associated with greater impairment. Within this overlap, clinicians frequently observe a subset of patients whose compulsive eating is organized around the pursuit of extreme fullness rather than palatability for specific trigger foods. Compulsive high-volume eating (CHVE) refers to recurrent, distressing episodes of consuming dangerously large volumes of food, often to the point of marked gastric distension. In some cases, the food is low-caloric or non-hedonic, and the dominant motivator is the interoceptive target state of extreme fullness rather than taste. This Perspectives article focuses on fullness-seeking as a high-volume pattern within binge eating disorder phenomenology that has received little attention in the food addiction literature. It extends prior work that framed volume addiction within compulsive high-volume eating as a public health issue. The focus here is clinical formulation, not the public health case. Evidence from reward learning, gut-brain signaling, gastrointestinal physiology, and neuroendocrinology suggests that this pattern may be rooted in binge eating disorder. It may identify a subset of patients with addiction-like dynamics. These cases may be better addressed when addiction-informed concepts and tools are integrated. It offers a physiologically grounded lens for combining eating disorder and addiction frameworks in a more coherent clinical approach.
Posted on

Parabilis Files for IPO, a Day After Signing Up-to-$2.3B Regeneron Collaboration

Parabilis Medicines, the developer of drugs and antibody-drug conjugates targeting historically undruggable protein targets and based on stabilized helical peptides or Helicons™, has filed for an initial public offering (IPO), joining a growing parade of companies seeking to raise capital by tapping into the improving market for first time biotech stocks.

The company’s IPO filing came a day after Parabilis inked an up-to-$2.3 billion-plus strategic research collaboration with Regeneron Pharmaceuticals to discover and develop an initial five candidates encompassing “antibody-Helicon conjugates,” a new form of antibody-drug conjugates aimed at challenging and historically undruggable targets.

Regeneron has agreed to purchase approximately $75 million of Parabilis common stock in a concurrent private placement, at 90% of the IPO price per share.

It’s too soon to know how much money Parabilis plans to raise through the IPO. The company’s Form S-1 registration statement, filed Tuesday with the U.S. Securities and Exchange Commission (SEC), includes a placeholder “$100 million” figure that will inevitably be revised, and doesn’t say how many shares will be sold. Parabilis has applied to list its shares on The Nasdaq Global Market under the ticker symbol “PBLS.”

It’s also too early to know how much of the proceeds will go toward the four priorities it highlighted in its registration statement. Two of the four priorities relate to Parabilis’ 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. Parabilis stated that it plans to continue ongoing clinical development of zolucatetide in desmoid tumors, including continuation of dose expansion and the launch of a Phase III registrational trial to topline data.

Parabilis also plans to continue ongoing clinical development of zolucatetide across several additional indications, including dose escalation and expansion in familial adenomatous polyposis (FAP); hepatocellular carcinoma, the most common type of primary liver cancer; and other rare tumors, with the aim of collecting data to support a registrational trial.

‘Expansive opportunity’

“We believe zolucatetide provides clinical validation of our first-in-industry Helicon approach and represents an expansive opportunity for medical and commercial impact,” Parabilis stated.

In addition, Parabilis plans to use IPO proceeds toward advancing its pipeline of additional programs—including its ERG protein degrader, an allosteric androgen receptor in its active state (ARON), and beta-catenin degraders—to Phase I clinical data; toward continued evolution of the Helicon platform for discovering and developing drug candidates; as well as toward general corporate purposes that include additional development efforts, working capital, and operating expenses.

According to Parabilis, zolucatetide has been evaluated in more than 150 patients to date and has generated positive clinical data in solid tumors characterized by alterations in the Wnt/beta-catenin pathway. In the drug’s lead indication of desmoid tumors, researchers have seen tumor reductions in 100% of patients with a 74% objective response rate (ORR) in patients who have had at least two post-baseline scans.

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.

Parabilis says its Helicon discovery platform allows it to precisely tune potency, selectivity, and pharmacologic properties by integrating ligands and additional functionalities at multiple positions. The platform integrates artificial intelligence (AI)- and physics-based computational modeling with high-throughput peptide synthesis and experimental screening.

“While our initial programs are focused on disrupting protein-protein interactions and inducing targeted protein degradation, we believe our platform can incorporate other advances in small molecule drug design and extend them to targets that are likely to remain out of reach for other modalities,” Parabilis stated.

Parabilis was founded in 2015 as FogPharma to commercialize technology developed in and inlicensed from the lab of Harvard University researcher and serial entrepreneur Gregory Verdine, PhD. The company, which rebranded itself into Parabilis in 2024, says it has generated proprietary datasets, comprising millions of data points for hundreds of thousands of Helicons across dozens of drug-like properties, following a decade of Helicon drug discovery.

‘Continuous learning loop’

“These data power a continuous learning loop that refines our models from target selection through lead optimization, enhancing our speed, precision, and ability to generate high quality molecules against difficult targets,” Parabilis explained. “As a result, our platform produces unique complex synthetic molecules at scale and a compounding advantage that we believe is difficult to replicate.”

If it carries out the planned IPO, Parabilis would be the 12th biotech to go public this year. The 11 IPO companies to date have raised a combined $3.491 billion, compared to the $1.556 billion raised by 11 companies this time last year. Six of the 11 companies have seen their shares rise since their initial offerings, led by the 520% share price increase of Veradermics, a developer of treatments for dermatology and aesthetic conditions that closed Wednesday at $105.32 a share.

This year’s largest IPO—and the largest of any biotech—was the $625 million offering of Kailera Therapeutics, a developer of therapies for obesity and weight management based on glucagon-like peptide receptor 1 (GLP-1) agonists, alone or in combination with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists.

Kailera last month completed what grew into a $718.75 million IPO last month that generated an estimated $662.1 million in net proceeds through the sale of 44,921,875 shares of common stock—including the exercise in full by underwriters of their option to purchase 5,859,375 additional shares—at the IPO price of $16 per share.

Should Parabilis’ planned IPO raise the placeholder $100 million amount, it would increase by 30% the $329.039 million in cash and cash equivalents that the company reported as of March 31.

Parabilis disclosed in its IPO filing that it ended the first quarter with a $45.316 million net loss, up 18% from its $38.342 million net loss of Q1 2025—as well as a net loss of $145.9 million for last year, up nearly 24% from its $117.9 million net loss for 2024. The company has no reported revenue.

Parabilis’ accumulated deficit rose 8% during Q1, to $586.82 million from $541.504 million at the end of 2025.

To fund its operations, Parabilis reported, it has raised a total $876.8 million as of March 31. That total consisted of $811.8 million from sales of its convertible preferred stock, $15 million in borrowings under a term loan and a $50 million Simple Agreement for Future Equity (SAFE).

The IPO comes just four months after Parabilis completed its last financing, an oversubscribed $305 million Series F round completed in January and co-led by investment firms RA Capital Management, Fidelity Management & Research Co., and Janus Henderson Investors.

Five investment firms were listed in the Form S-1 as underwriters for the IPO: Leerink Partners, BofA Securities, Evercore ISI, Guggenheim Securities, and LifeSci Capital.

The post Parabilis Files for IPO, a Day After Signing Up-to-$2.3B Regeneron Collaboration appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

Enzymes Involved in Cholesterol Transport May Point to New Cancer Therapies

Some types of cancer have a relentless appetite for the metabolite cholesterol, using as much as they can access to accelerate their growth beyond the capabilities of normal cells. Research by scientists at Sanford Burnham Prebys Medical Discovery Institute and collaborators at the University of Illinois Chicago have now unveiled a potential method for turning the table on these tumors by subverting their cholesterol cravings.

The researchers’ studies, in mice and in human cancer cells, revealed new insights into enzymes known as phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) that help move cholesterol around cells. The researchers showed that without the help of these enzymes, a cholesterol traffic jam occurs, blocking the cancer cell’s ability to fuel tumor growth.

Headed by Brooke Emerling, PhD, the director of and associate professor in the Cancer Metabolism and Microenvironment Program at the Sanford Burnham Prebys NCI-Designated Cancer Center, the team reported on its findings in Science Advances, in a paper titled “Noncanonical PI(4,5)P2 coordinates lysosome positioning through cholesterol trafficking.”

The TP53 gene is mutated in roughly half of all cancers. Emerling and first author Ryan Loughran, PhD, a postdoctoral associate in the Emerling lab, focus on difficult-to-treat forms of breast cancer, where TP53 mutations are found in more than 84% of triple-negative breast cancers and three of every four HER2-amplified breast cancers.

Cancer cells with a mutation in the tumor-suppressing TP53 gene are known to produce extra cholesterol. This may make them more vulnerable to starvation if scientists can put a stop to the steady supply of the lipid. “We need more ways to treat cancers with this common mutation,” said Emerling. “One of our main goals with this work was to find new treatment possibilities for the large subset of breast cancers harboring TP53 mutations,” said Loughran. “We recognized a real opportunity in targeting the enzymes that control cholesterol transport, especially since cancer cells depend on this process far more than normal cells do.”

To better understand how to turn these cancers’ cholesterol consumption into a weakness, the research team turned to a family of cell membrane lipids known as phosphoinositides and the kinase enzymes that regulate them. The investigators had shown that a branch of the lipid enzyme family known as PI5P4Ks were required for the growth of cancers with TP53 mutations in mice, and they suspected that this tumor prevention was due to the enzymes’ role relocating cholesterol in the cell. “Our group has shown that suppression of the most catalytically active PI5P4K isoforms (α and β) in TP53-deficient cancer cells inhibits proliferation, and the deletion of these enzymes in Trp53-knockout mice confers protection from tumorigenesis,” the investigators wrote.

“Normally, when mice lose TP53 as the guardian of their genomes, they are fated to die from cancer in four-to-eight months,” said Emerling. “When you delete these kinases, the animals are 100% protected and never develop a tumor—and cholesterol turned out to be one of the missing pieces in this puzzle.”

The scientists conducted experiments in mouse and human cancer cells showing that PI5P4Ks influenced the movement and behavior of organelles that carry cholesterol around our cells. In cancer cells with TP53 mutations and PI5P4Ks, cholesterol-laden lysosomes were found near the exterior cell membrane. Without PI5P4Ks, lysosomes remained in the interior of the cells, near the nucleus.

Location is critical for lysosomes transporting cholesterol. While positioned near the edge of the cell, lysosomes and their cargo are in proximity with many receptor proteins, enzymes and signaling molecules that exist around the cell membrane. This includes mechanistic target of rapamycin complex 1 (mTORC1), an enzyme that governs cell growth and runs amok in cancer. “When lysosome positioning is biased towards the cell nucleus, mTORC1 activation is suppressed,” said Loughran. “This connects directly to our previous work, where we found that the loss of these kinases triggers starvation-like states in cancer cells. “When PI5P4Ks are absent, the link between lysosomal cholesterol and mTORC1 is compromised, a bit like two ships passing in the night.”

The change in lysosome position towards the cell’s interior that occurs without PI5P4Ks reduced interaction with mTORC1 and prevented it from sending signals associated with tumor growth. “The mTOR activation pathway is really what drives tumorigenesis, and so mTOR is an important target for cancer drug development,” said Emerling. “If we can target mTOR activity in aggressive cancers by blocking the sensing of cholesterol, that would be a promising treatment strategy.”

In their report the authors noted in summary, “The dependence of p53-deficient tumor cells on PI5P4Ks has been previously attributed to their roles as critical modulators of cellular stress responses, including protection from oxidative stress, maintenance of mitochondrial health, and regulation of autophagy. We now identify a previously undescribed role for PI5P4Ks in maintaining lysosomal cholesterol homeostasis and mTORC1 signaling.”

Previous research has looked at the use of statins as cancer drugs due to their ubiquity and safety as treatments for patients with high cholesterol. While more research is needed, studies so far suggest that tumors eventually acquire resistance to statins. “While cholesterol synthesis inhibitors such as statins have shown initial success, their efficacy is often compromised by the development of acquire resistance,” the team noted in the paper. “Consequently, strategies are being explored to disrupt cholesterol homeostasis more comprehensively by inhibiting its synthesis and intracellular transport.”

Loughran added, “It is important for us to find other ways to more comprehensively cut cancer cells off from cholesterol to impede their growth.” Emerling further stated, “We’ll continue to explore blocking PI5P4Ks as a more targeted approach tailored to how tumors operate.”

The post Enzymes Involved in Cholesterol Transport May Point to New Cancer Therapies appeared first on GEN – Genetic Engineering and Biotechnology News.