enGene (NASDAQ: ENGN) stock suffered an 83% plunge this past week that reflects just how competitive the field is among drug candidates for nonmuscle invasive bladder cancer (NMIBC)—and how questions over clinical data are enough to send investors scurrying to sell their shares.

enGene shares cratered 81% Thursday from $8.85 to $1.72, then fell another 13% Friday, reaching a 52-week low as it finished the week at $1.50.

The sharp falloff followed enGene reporting updated data from its Phase II LEGEND trial (NCT04752722) assessing its nonviral gene therapy candidate detalimogene voraplasmid in high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive NMIBC patients with carcinoma in situ (CIS) with or without concomitant papillary disease (CIS±papillary). The data showed a drop in response rates from a November 2025 readout, falling short of company and Wall Street expectations.

As of the April 21 data cutoff, 67 of 124 evaluable patients treated with detalimogene (formerly EG-70) achieved a 54% complete response (CR) at any time, a rate that fell to 43% (52 of 121 evaluable patients) CR rate at six months. That compares with the 63% CR at any time and 62% CR rate at six months shown for the first 62 patients assessed, as announced by enGene in November 2025.

Also, detalimogene showed a nine-month CR rate of 32.7%, which fell to 13.3% at 12 months after treatment. Engene said it will present its data at the American Urological Association Annual Meeting (AUA 2026), set for May 15–18 in Washington, DC.

“While durability outcomes to date are not what we hoped, these data are preliminary,” enGene president and CEO Ron Cooper stressed in a statement. “We are focused on evaluating the totality of the data as it evolves and plan to continue to engage with the FDA and the medical community.”

Speaking to analysts, Cooper added: “The data are not yet fully mature, and the durability picture is incomplete. We plan to await longer-term durability data for all of Cohort 1 in the second half of the year and continue our ongoing discussion with the FDA regarding both our statistical analysis plans and plans for potential BLA filing.”

“Below key benchmarks”

At least two analysts warned that the updated data will make it harder for enGene to compete with other developers of NMIBC treatments now in the clinic.

“Durability now screens below key benchmarks in the setting, which makes it hard for us to underwrite meaningful commercial upside for detalimogene in what will be a crowded mkt, where ~40% 12‑mo CR is the bar to clear,” cautioned Maury Raycroft, PhD, equity analyst with Jefferies, in a research note.

Raycroft slashed enGene’s 12-month price target 82% from $28 to $5. More ominously, Raycroft chopped Jefferies’ peak sales forecasts for detalimogene by 79%—from the $1.7 billion forecasted for the gene therapy across CIS±papillary, papillary‑only, and BCG‑naïve NMIBC, to $350 million for CIS±papillary alone.

The NMIBC treatment space has expanded in recent years as established drugs like the cancer immunotherapy blockbuster Keytruda® (pembrolizumab), marketed by Merck & Co. (NYSE: MRK), have been joined on the market by newer therapies.

One is Johnson & Johnson (NYSE: JNJ)’s Inlexzo (gemcitabine), an intravesical drug releasing system (iDRS) designed to provide sustained local delivery of a cancer treatment into the bladder. Two other newer therapies are Adstiladrin® (nadofaragene firadenovec-vncg), a nonreplicating adenoviral vector-based gene therapy indicated for high-risk BCG-unresponsive NMIBC with CIS±papillary and marketed by privately held Ferring Pharmaceuticals (which licensed the drug from another private company, FKD Therapies, in 2018); and ImmunityBio (NASDAQ: IBRX)’s interleukin-15 (IL-15) receptor agonist Anktiva® (nogapendekin alfa inbakicept-pmln), indicated with BCG. ImmunityBio is part of the privately held NantWorks portfolio of companies.

Those marketed drugs are expected to be joined over the next couple of years by candidates being developed by:

• CG Oncology (NASDAQ: CGON), which is expected to report topline data from the Phase III PIVOT-006 trial (NCT06111235) of cretostimogene grenadenorepvec, also called CG0070, as an adjuvant therapy in intermediate-risk NMIBC. First results on the combo of cretostimogene with gemcitabine from the Phase II CORE-008 trial (NCT06567743) are to be presented at AUA 2026.
• Relmada Therapeutics (NASDAQ: RLMD), which will present two abstracts focused on its NDV-01, a sustained-release intravesical formulation of gemcitabine and docetaxel being developed to treat NMIBC at AUA 2026. Relmada plans to present nine-month complete response data from its open-label Phase II trial (NCT06663137) assessing NDV-01 in high-risk NMIBC, as well as discuss its open-label Phase III BOOST trial (NCT07313891), which is evaluating NDV-01 vs. surveillance following transurethral resection of bladder tumor (TURBT).

Mani Foroohar, MD, senior managing director, genetic medicines, and a senior research analyst with Leerink Partners, noted that enGene’s 54% any time and 43% six-month updated CR rates lagged behind those of three competitors: Anktiva (71% and 56%), cretostimogene (75.5% and 64%), and Inlexzo (82% and 59%). However, he added that Adstiladrin was more comparable to detalimogene, which showed rates of 51% and 41%.

Competitive position concern

“Weaker data in recent patient cohorts and lower-than-expected durability trends undermine our confidence in [detalimogene]’s competitive position and essentially foreclose the possibility of closing the efficacy gap with CGON, JNJ, etc., in a later LEGEND update,” Foroohar wrote in a research note.

“With shares trading at a level pricing in program failure, investor focus will center on cohort consistency, data evolution with longer follow-up, and FDA interpretation of the totality of the dataset (questions that will take time to address and will not be resolved prior to full LEGEND data/subsequent regulatory engagement,” Foroohar added.

Like Raycroft, Foroohar also now projects $350 million in unadjusted peak year sales for detalimogene, shredding his firm’s projection by 65% from $1 billion.

“From here, investor discussion will center on whether longer follow-up and additional cohort maturation can stabilize efficacy trends ahead of further FDA engagement in 2H26.”

enGene and Cooper insist that detalimogene is more than up to the challenge of competing with other NMIBC treatments. Of the 52 patients who responded at six months, 37 of 44 patients who had a nine-month assessment were in CR (an additional eight patients are pending evaluation), while 13 of 22 patients who had a 12-month assessment were in CR (an additional 11 patients are pending evaluation).

Among patients who showed the 43% six-month CR rate, 14% (6 of 43) successfully converted from non-CR to CR post re-induction.

The company cited other data from the LEGEND trial showing that the progression rate to muscle-invasive or advanced disease was 3.2%, a figure enGene calls low. Detalimogene was generally well tolerated, the company added, with 55% of patients having experienced a treatment-related adverse event (TRAE), mostly mild (Grade 1 and 2), though six patients (4.8%) reported a Grade 3 TRAE.

“These updated data continue to reinforce the favorable safety and tolerability profile of detalimogene and its clinical activity in a heavily pretreated, high-risk NMIBC patient population with limited therapeutic options,” enGene’s Cooper stated. “Importantly, the low rate of progression to muscle-invasive disease leaves patients eligible for other bladder-sparing therapies.”

Detalimogene’s favorable safety profile was also acknowledged by Jefferies’ Raycroft: “We continue to view this administrability/safety profile as a core differentiator vs other intravesical gene/immune constructs (and a key adoption lever), even as durability to date is tracking below expectations.”

IPO roundup: Odyssey raises $304M, drops 9%

Odyssey Therapeutics (NASDAQ: ODTX) raised $304 million in gross proceeds through an upsized initial public offering (IPO) by selling 15.5 million shares priced Thursday at $18 a share, the top of its $16–$18 range, and well above the 13.2 million shares it disclosed in its prospectus just before the offering. Concurrently, an affiliate of TPG Life Sciences Innovations purchased 1.39 million shares at the IPO price, raising another $25 million for Odyssey.

But on their first full day of trading on Friday, Odyssey’s shares fell 9%, closing at $16.42, as investors deemed the upsizing to be aggressive.

Odyssey, a developer of targeted therapies for autoimmune and inflammatory diseases, said it would use approximately $135 million in IPO proceeds to advance its lead candidate, the oral small molecule RIPK2 scaffolding inhibitor OD-001, through 12-week induction readouts from its planned Phase IIa combination trial and Phase IIb monotherapy trial in ulcerative colitis.

Plans also call for using approximately $50.0 million of proceeds to advance Odyssey’s oral small molecule SLC15A4 inhibitor OD-002 through IND-enabling activities and a planned Phase I/IIa trial; and the rest for additional discovery, preclinical, and clinical activities for disclosed or future programs, enabling capabilities, as well as general corporate purposes, working capital, and other capital expenditures.

An option to purchase up to an additional 2.325 million shares at the IPO price is held by Odyssey’s IPO underwriters: J.P. Morgan, TD Cowen, and Cantor are joint book-running managers, while Wedbush PacGrow and Oppenheimer are co-lead managers.

The Odyssey IPO is one of four biotech IPOs emerging in recent weeks:

• Hemab Therapeutics Holdings (NASDAQ: COAG), based in Cambridge, MA, and Copenhagen, closed its IPO on May 4, having raised $346.7 million by selling 19,262,500 shares at $18 a share—the original offering of 16.75 million shares, plus all 2,512,500 shares for which underwriters held purchase options. Goldman Sachs, Jefferies, and Evercore ISI were joint book-running managers; Wedbush PacGrow was the lead manager. Shares have since jumped 40%, closing Friday at $25.12.
• Seaport Therapeutics (NASDAQ: SPTX) of Boston garnered $254.88 million on April 30 by selling 14.16 million shares at $18 a share. Seaport’s underwriters have a 30-day option to buy an additional 2.124 million shares at the IPO price less underwriting discounts and commissions. Goldman Sachs, J.P. Morgan, Leerink Partners, Citigroup, and Stifel are joint book-running managers. Shares have since slipped 11%, closing Friday at $16.05.
• A day earlier, Avalyn Pharma (NASDAQ: AVLN), also of Boston, launched an IPO that garnered $300 million by selling 16,666,667 shares at $18 a share—and revived the market of biotech initial offerings after a lull during March and early April. Avalyn ultimately racked up $345 million in gross proceeds after its underwriters exercised in full their option to buy 2.5 million more shares at the IPO price. Morgan Stanley, Jefferies, Evercore ISI, and Guggenheim Securities were joint book-running managers. Shares have since vaulted 52%, closing Friday at $27.33.

Leaders and laggards

• Atara Biotherapeutics (NASDAQ: ATRA) shares nearly doubled, leaping 92% from $5.15 to $9.93 Thursday after saying its partner Pierre Fabre Pharmaceuticals (PFP) had a productive Type A meeting with FDA officials to discuss an approval path for tabelecleucel (tab-cel). PFP’s Biologics License Application (BLA) has been rejected twice by the agency through Complete Response Letters, the most recent one in January. The FDA, Atara said, agreed that a single-arm study with an “appropriate” historical control, conducted in a pre-specified manner, “could serve as an adequate and well-controlled study and provide safety and efficacy data in support of a future marketing application.” Atara said PFP intends to submit updated data with longer follow-up from the pivotal Phase III ALLELE trial (NCT03394365) assessing tabelecleucel in adults and children ages 2+ with relapsed/refractory Epstein-Barr virus plus post-transplant lymphoproliferative disease (PTLD) following solid organ transplant or hematopoietic cell transplant.
• Entrada Therapeutics (NASDAQ: TRDA) shares nosedived 57% Thursday from $16.03 to $6.85 after the genetic medicine developer reported topline data from Cohort 1 of the multiple ascending dose (MAD) portion of the Phase I/II ELEVATE-44-201 trial (NCT07037862) that the company called positive, but which disappointed investors. Entrada said its Duchenne muscular dystrophy (DMD) candidate ENTR-601-44 met the trial’s primary objective by showing favorable safety and tolerability, no discontinuations, and no serious adverse events. But data showed an increase of 2.36% in dystrophin from a baseline of 4.00%—compared to the 10% increase sought by analysts such as Myles R. Minter, PhD, of William Blair. “Management is attributing the miss on biomarker data to lower-than-expected drug exposure,” Minter wrote, “likely due to the transition from dosing adults to juvenile patients.” Entrada cited other positive data, such as lower plasma exposure in Cohort 1 participants ages 6–17 vs. healthy adult volunteers; and markers of kidney function via eGFR, Cystatin C, and magnesium all falling within normal ranges and comparable to placebo.
• Moderna (NASDAQ: MRNA) shares rose 12% Friday from $48.54 to $54.35 after a news report that the messenger RNA (mRNA)-based vaccine developer was researching vaccines designed to protect against hantaviruses. In a statement, Moderna disclosed that it has carried out early-stage vaccine research on hantaviruses with the U.S. Army Medical Research Institute of Infectious Diseases and is also partnering with the Vaccine Innovation Center at Korea University College of Medicine on a potential jab. “These efforts are early-stage and ongoing and reflect Moderna’s broader responsibility to develop countermeasures against emerging infectious diseases,” Moderna told Bloomberg News. As of Friday, the World Health Organization (WHO) has reported eight cases of hantavirus, including three deaths, among passengers aboard the MV Hondius cruise ship, traveling between Argentina and the Canary Islands in the Atlantic Ocean.
• Viridian Therapeutics (NASDAQ: VRDN) shares jumped 33% from $14.06 to $18.75 Tuesday after the autoimmune and rare disease drug developer announced positive topline data from the Phase III REVEAL‑2 trial (NCT06625398) assessing elegrobart in chronic thyroid eye disease (TED). Doses of elegrobart given every 4 and 8 weeks achieved what Viridian called “highly statistically significant” 50% and 54% proptosis responder rates (PRR) at week 24, respectively, vs. 15% for placebo. Elegrobart is a subcutaneously delivered, half‑life‑extended monoclonal antibody targeting the insulin‑like growth factor‑1 receptor (IGF‑1R). Viridian said it remains on track to submit a Biologics License Application (BLA) to the FDA for elegrobart in Q1 2027. Viridian cashed in on the news by launching underwritten public offerings of $150 million in convertible senior notes due 2032 and $100 million in Series B nonvoting convertible preferred stock.

The post StockWatch: enGene Shares Crater on Declines in Complete Response Rates to Bladder Cancer Therapy appeared first on GEN – Genetic Engineering and Biotechnology News.

For decades, physicians and scientists have thought that metformin, a biguanide drug that is prescribed for millions of people worldwide for type 2 diabetes (T2D), mainly targets the liver to suppress glucose production. A Northwestern University-led study in mice has now found that this “wonder drug” instead acts primarily on the gut, and prevents glucose levels from rising in the blood by driving glucose utilization inside cells lining the intestine.

The research found that metformin slows mitochondrial energy production in gut cells by inhibiting mitochondrial complex I in the intestinal epithelium. This then “co-opts” the intestines to function as a glucose sink, forcing the intestine to metabolize extra sugar. The study also found that another biguanide drug, phenformin, and the structurally unrelated supplement berberine, which is known as “nature’s Ozempic,” appear to engage the same pathway in the gut as does metformin.

The preclinical findings could help to explain several gut-related clinical effects in people who take metformin and suggest that modulating mitochondrial metabolism in the gut may represent an effective strategy for controlling blood sugar. “Metformin essentially helps the intestine suck the glucose out of the bloodstream, which further highlights that the gut plays a major role in regulating blood sugar levels,” said corresponding author Navdeep Chandel, PhD, professor of biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine.

Chandel is senior and co-corresponding author of the researchers’ published paper in Nature Metabolism, titled “Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycaemic control.” Chandel is also the David W. Cugell, MD, Professor of Medicine (Pulmonology and Critical Care), Biochemistry and Molecular Genetics, and an investigator with the Chan Zuckerberg Initiative. The study’s first author is Zach Sebo, PhD, a postdoctoral fellow in the Chandel lab who will soon start his own research group at the University of Kansas School of Medicine.

Metformin is the most widely prescribed medication for type 2 diabetes and the biguanide class drug approved by the FDA, the authors wrote. However, they noted, “Despite its extensive use, the mechanisms underlying its clinical effects, including attenuated postprandial glucose excursions and elevated intestinal glucose uptake, remain unclear.”

The body relies on glucose as a fast and versatile fuel, but too much glucose can lead to insulin resistance and ultimately damage blood vessels and organs. The newly reported study builds on findings from previous work in Chandel’s lab, which found that metformin lowers blood sugar by blocking a specific part of the cell’s energy-making machinery, mitochondrial complex I, a key enzyme in cellular respiration. The research reported in Nature Metabolism extends that work by pinpointing the specific tissue targeted by metformin.

The study used a mouse model genetically engineered to express a yeast enzyme (NDI1) that mimics mitochondrial complex I but is resistant to inhibition by metformin. By expressing NDI1 specifically in intestinal cells, those gut cells resisted metformin’s effects. In these mice, the drug’s ability to lower blood glucose was significantly reduced, demonstrating that inhibition of mitochondrial complex I in the gut is a key driver of its therapeutic action. “In this study, we show how metformin exerts multiple clinical effects through selective inhibition of mitochondrial complex I in the intestinal epithelium,” they wrote.

Metformin is currently the only FDA-approved biguanide drug, but the team found that another biguanide, phenformin, which had previously been used to control blood glucose but was then withdrawn, also lowered blood glucose through the same mechanism. The findings suggest that directing drugs or supplements to the gut could be an effective strategy for controlling blood sugar, Chandel said. Sebo added, “Our study suggests that revisiting assumptions about metformin’s mechanism may offer a more detailed understanding of how it works.”

The study revealed unexpected parallels with berberine, a popular plant-derived OTC supplement that is often used to control blood sugar. Berberine has recently gained attention on social media as “nature’s Ozempic,” though experts caution that evidence is still limited, and it should not be used as a substitute for approved medications. The study by Chanel and colleagues has now found that berberine appears to engage the same pathway as metformin in the intestine. “Thus, we identify mitochondrial complex I in intestinal epithelium as a shared and essential therapeutic target for metformin, phenformin, and berberine,” the authors stated.

“Metformin has decades of clinical evidence behind it, whereas supplements like berberine are far less rigorously tested,” Chandel said. “If you’re going to use berberine, you may as well use the real deal.”

The study results may help to explain clinical observations among people who take metformin. According to Chandel, individuals who take metformin tend to have lower blood sugar after meals, and the study suggests that metformin turns the gut into a “sponge” that soaks up extra sugar. Individuals taking metformin also tend to have lower levels of circulating citrulline, which is made only by mitochondria in small intestine cells. If metformin inhibits mitochondria, citrulline production drops. Taking metformin also increases levels of GDF15, a hormone linked to reduced appetite and weight loss. The gut senses energy stress and sends out GDF15, which tells the brain to eat less and adjust metabolism.

“In addition to enhanced intestinal glucose utilization and blood glucose clearance, this mechanism accounts for metformin-induced citrulline depletion, improved postprandial glycaemia, and elevated lactoyl-phenylalanine (Lac-Phe) and growth differentiation factor 15 (GDF15) levels—all of which are definitive clinical outcomes caused by metformin treatment,” the authors wrote in summary.

“People have always wondered how one drug can do 10 things,” Chandel said. “Well, it can do that if the drug is hitting a big node in a cell, and hitting mitochondria in a cell is a big node. So, if you can get into those cells and inhibit mitochondria, it’s going to have huge effects.”

The post Diabetes Drug Metformin’s Blood Glucose-Lowering Effects Tied to Action on Gut Cells appeared first on GEN – Genetic Engineering and Biotechnology News.

Scientists at the University of Rochester pulled off a remarkable experiment: they transferred a longevity-related gene from the famously long-lived naked mole rat into mice, and the mice ended up healthier and lived longer. The special gene boosts production of a substance called high molecular weight hyaluronic acid, which appears to protect against cancer, reduce inflammation, and support healthier aging. The modified mice showed stronger resistance to tumors, healthier guts, and lower levels of age-related inflammation.