作者: Chuter, Benton G. ; Cui, Qi N. ; Halfpenny, William ; Weinreb, Robert N. ; Baxter, Sally L. ; Cui, Qi N ; Weinreb, Robert N ; Baxter, Sally L ; Hallaj, Shahin ; Chuter, Benton G

PURPOSE:

This study evaluates the effects of glucagon-like peptide-1 receptor (GLP-1R) agonists on intraocular pressure (IOP).

DESIGN:

Retrospective clinical cohort study.

METHODS:

The University of California Health Data Warehouse was queried for patients exposed to GLP-1R agonists or other oral antidiabetics. A total of 1247 glaucoma surgery and treatment naïve eyes of 626 patientson GLP-1R agonists and 1083 glaucoma surgery and treatment naïve eyes of 547 patients on other oral antidiabetics were included. Index date was defined as the date of first exposure to the medication. Eyes with at least one pre-exposure and one post-exposure tonometry records within 365 days of the index date were included. Clinical and laboratory data were extracted. Eyes were excluded upon exposure to glaucoma hypotensive medication or glaucoma surgery. The primary outcome measure was ∆IOP after exposure, which was analyzed using a paired t test and generalized estimating equations (GEE) RESULTS: The median age was 66.2 years [IQR = 18.3]; 607 (51.7%) were female, and 667 (56.9%) were Caucasian. Median pre-exposure IOP, hemoglobin A1c, and body mass index were 15.2 mm Hg [IQR = 3.8], 7.5 [IQR = 2.4], and 29.8 [IQR = 9.4], respectively. A total of 776 individuals (66.1%) had diabetes, with the median number of active oral antidiabetics being 1.0 [IQR = 1.0], and 441 (37.5%) being insulin users. Several pre-exposure characteristics differed between the groups. The mean ∆IOP was -0.4 ± 2.8 mm Hg (paired t test P < .001) and -0.2 ± 3.3 mm Hg (paired t test P = .297) in the GLP-1R agonist and other antidiabetics groups, respectively. Pre-exposure IOP was the only independent predictor of ΔIOP in multivariable GEE. Sensitivity analyses yielded similar results.

CONCLUSIONS:

Although GLP-1R agonists were significantly associated with a decrease in IOP in the paired analysis, they were not associated with ΔIOP in multivariable GEE. Moreover, the difference in ΔIOP between the two groups was small.

2024-12-01·CANCER AND METASTASIS REVIEWS

The effect of GLP-1R agonists on the medical triad of obesity, diabetes, and cancer

Review

作者: Arabi, Batoul ; Ibrahim, Raghad Sabaawi ; Ibrahim, Shahad Sabaawi ; Shakibaei, Mehdi ; Büsselberg, Dietrich ; Brockmueller, Aranka

Abstract:

Glucagon-like peptide-1 receptor (GLP-1R) agonists have garnered significant attention for their therapeutic potential in addressing the interconnected health challenges of diabetes, obesity, and cancer. The role of GLP-1R in type 2 diabetes mellitus (T2DM) is highlighted, emphasizing its pivotal contribution to glucose homeostasis, promoting β-cell proliferation, and facilitating insulin release. GLP-1R agonists have effectively managed obesity by reducing hunger, moderating food intake, and regulating body weight. Beyond diabetes and obesity, GLP-1R agonists exhibit a multifaceted impact on cancer progression across various malignancies. The mechanisms underlying these effects involve the modulation of signaling pathways associated with cell growth, survival, and metabolism. However, the current literature reveals a lack of in vivo studies on specific GLP-1R agonists such as semaglutide, necessitating further research to elucidate its precise mechanisms and effects, particularly in cancer. While other GLP-1R agonists have shown promising outcomes in mitigating cancer progression, the association between some GLP-1R agonists and an increased risk of cancer remains a topic requiring more profound investigation. This calls for more extensive research to unravel the intricate relationships between the GLP-1R agonist and different cancers, providing valuable insights for clinicians and researchers alike.

2024-11-01·Molecular Metabolism

The GLP-1 medicines semaglutide and tirzepatide do not alter disease-related pathology, behaviour or cognitive function in 5XFAD and APP/PS1 mice

Article

作者: Drucker, Daniel J ; Matthews, Dianne ; Baggio, Laurie L. ; Cui, Fiona ; Forny Germano, Leticia ; Drucker, Daniel J. ; Wong, Chi Kin ; Rittig, Nikolaj ; Koehler, Jacqueline A ; Koehler, Jacqueline A. ; Cao, Xiemin ; Baggio, Laurie L

OBJECTIVE:

The development of glucagon-like peptide-1 receptor (GLP-1R) agonists for the treatment of type 2 diabetes and obesity has been accompanied by evidence for anti-inflammatory and cytoprotective actions in the heart, blood vessels, kidney, and brain. Whether GLP-1R agonists might be useful clinically for attenuating deterioration of cognitive dysfunction and reducing the progression of Alzheimer's disease remains uncertain.

METHODS:

Here we evaluated the actions of semaglutide and tirzepatide, clinically distinct GLP-1 medicines, in two mouse models of neurodegeneration.

RESULTS:

Semaglutide reduced body weight and improved glucose tolerance in 12-month-old male and female 5XFAD and APP/PS1 mice, consistent with pharmacological engagement of the GLP-1R. Nevertheless, amyloid plaque density was not different in the cerebral cortex, hippocampus, or subiculum of semaglutide-treated 12-month-old 5XFAD and APP/PS1 mice. IBA1 and GFAP expression were increased in the hippocampus of 5XFAD and APP/PS1 mice but were not reduced by semaglutide. Moreover, parameters of neurobehavioral and cognitive function evaluated using Open Field testing or the Morris water maze were not improved following treatment with semaglutide. To explore whether incretin therapies might be more effective in younger mice, we studied semaglutide and tirzepatide action in 6-month-old male and female 5XFAD mice. Neither semaglutide nor tirzepatide modified the extent of plaque accumulation, hippocampal IBA1+ or GFAP+ cells, or parameters of neurobehavioral testing, despite improving glucose tolerance and reducing body weight. mRNA biomarkers of inflammation and neurodegeneration were increased in the hippocampus of male and female 5XFAD mice but were not reduced after treatment with semaglutide or tirzepatide.

CONCLUSIONS:

Collectively, these findings reveal preservation of the metabolic actions of two GLP-1 medicines, semaglutide and tirzepatide, yet inability to detect improvement in structural and functional parameters of neurodegeneration in two mouse models of Alzheimer's disease.

项与 TERN-601 相关的新闻（医药）

2024-11-12

·GlobeNewswire-Health Care

Terns Pharmaceuticals Reports Third Quarter 2024 Financial Results and Corporate Updates

Interim data from initial dose escalation cohorts of Phase 1 CARDINAL trial evaluating TERN-701 (allosteric BCR-ABL tyrosine kinase inhibitor) in chronic myeloid leukemia (CML) expected in early December 2024 Plans to initiate Phase 2 clinical trial for TERN-601 in obesity in early 2Q25 with initial 12-week data expected in 2H25 Cash, cash equivalents and marketable securities of $372.8 million, including $172.7 million equity raise in September, expected to provide runway into 2028 FOSTER CITY, Calif., Nov. 12, 2024 (GLOBE NEWSWIRE) -- Terns Pharmaceuticals, Inc. (“Terns” or the “Company”) (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology and obesity, today reported financial results for the third quarter ended September 30, 2024, and provided corporate updates. “Our progress in the third quarter was highlighted by the compelling topline results from our Phase 1 study of TERN-601, which demonstrated class-leading potential as a differentiated, once-daily, oral GLP-1R agonist for the treatment of obesity and supports its rapid advancement into Phase 2 studies,” stated Amy Burroughs, chief executive officer of Terns. “We are looking forward to sharing interim dose escalation data from the Phase 1 CARDINAL trial of TERN-701 as a treatment for chronic myeloid leukemia (CML) and expect this early look at safety, tolerability and signals of efficacy to reinforce its potential as a best-in-class allosteric for the treatment of CML. Importantly, our successful equity raise underscores the strong support for our promising pipeline of differentiated small molecules, funds Terns through multiple catalysts across our clinical development programs and extends our cash runway into 2028.” Recent Pipeline Developments and Anticipated Milestones TERN-701: Oral, allosteric BCR-ABL tyrosine kinase inhibitor (TKI) for chronic myeloid leukemia (CML) Interim data from initial dose escalation cohorts in Terns’ ongoing Phase 1 CARDINAL study of TERN-701 in CML expected in early December 2024 CARDINAL is a global, multicenter, open-label, two-part Phase 1 clinical trial to evaluate the safety, pharmacokinetics (PK) and efficacy of TERN-701 in patients with previously treated CMLThe Company expects to share interim dose escalation data from the CARDINAL study, including safety, tolerability and early signals of efficacy In August, Terns hosted a TERN-701 webinar event focused on interpreting early datasets in CML TERN-601: Oral, small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist for obesity Terns plans to initiate a Phase 2 clinical trial in early second quarter of 2025 with initial 12-week data expected in the second half of 2025 The trial will begin with a 12-week portion to optimize dose titration and inform subsequent cohorts In September, Terns announced positive safety and 28-day weight loss data from the Phase 1 first-in-human clinical trial of TERN-601 in obese and overweight participants The results showed TERN-601 was well tolerated and demonstrated dose-dependent, statistically significant mean weight loss up to 5.5% (4.9% placebo adjusted) over 28 days67% of study participants lost 5% or more of their baseline body weight at the highest dose of 740 mg once-daily (QD)TERN-601 exhibited distinct properties for an oral GLP-1R agonist Low solubility and high gut permeability allowed for prolonged absorption and sustained target coverage and a flat PK curve, while high drug levels in the gut wall may lead to robust GLP-1R activation in the gut triggering satiety centers in the brainLow free fraction in circulation, combined with the flat PK curve, may contribute to TERN-601's tolerability profile at higher target doses than other oral GLP-1R agonists TERN-601 was well-tolerated with no treatment-related dose interruptions, reductions, or discontinuations even with rapid dose titration TERN-501: Oral, thyroid hormone receptor-beta (THR-β) agonist In June, Terns presented new preclinical data at the American Diabetes Association (ADA) 84th Scientific Sessions supporting TERN-501 in combination with a GLP-1 receptor agonist for obesity Preclinical findings demonstrated TERN-501 in combination with semaglutide significantly enhanced weight loss and showed proportionally greater loss of fat mass relative to lean mass compared to semaglutide aloneSupports the potential for TERN-501 as a combination partner for injectable and oral GLP-1 agonists for use in obesity and other metabolic disordersThe full poster is available on Terns’ scientific publications website Terns continues to evaluate opportunities for TERN-501 in metabolic diseases TERN-800 Series: Oral, small-molecule glucose-dependent insulinotropic polypeptide receptor (GIPR) agonist Discovery efforts are ongoing for small molecule GIPR modulators for obesity, which have the potential for combination with GLP-1 receptor agonists, such as TERN-601Terns is prioritizing its discovery efforts on nominating a GIPR antagonist development candidate based on in-house discoveries and growing scientific rationale supporting the potential of GLP-1 agonist/GIPR antagonist combinations for obesity Corporate Updates In September, Terns completed an upsized public offering of 14,064,048 shares of its common stock and 2,380,952 pre-funded warrants, generating gross proceeds of approximately $172.7 million before deducting underwriting discounts and commissions and other offering expenses, which extends the Company’s cash runway into 2028In July, Terns appointed Elona Kogan as Chief Legal Officer Third Quarter 2024 Financial Results Cash Position: As of September 30, 2024, cash, cash equivalents and marketable securities were $372.8 million, as compared with $263.4 million as of December 31, 2023. Based on its current operating plan, Terns expects these funds will be sufficient to support its planned operating expenses into 2028. Research and Development (R&D) Expenses: R&D expenses were $15.2 million for the quarter ended September 30, 2024, as compared with $14.8 million for the quarter ended September 30, 2023. General and Administrative (G&A) Expenses: G&A expenses were $9.8 million for the quarter ended September 30, 2024, as compared with $18.4 million for the quarter ended September 30, 2023. Net Loss: Net loss was $21.9 million for the quarter ended September 30, 2024, as compared with $29.8 million for the quarter ended September 30, 2023. Financial Tables Terns Pharmaceuticals, Inc. Condensed Consolidated Statements of Operations (Unaudited; in thousands except share and per share amounts) Three Months EndedSeptember 30, Nine Months EndedSeptember 30, 2024 2023 2024 2023 Operating expenses: Research and development $15,169 $14,831 $52,108 $46,038 General and administrative 9,770 18,353 23,814 32,462 Total operating expenses 24,939 33,184 75,922 78,500 Loss from operations (24,939) (33,184) (75,922) (78,500)Interest income 3,088 3,480 9,146 9,568 Other expense, net (32) (5) (58) (69)Loss before income taxes (21,883) (29,709) (66,834) (69,001)Income tax expense (62) (58) (220) (190)Net loss $(21,945) $(29,767) $(67,054) $(69,191) Net loss per share, basic and diluted $(0.28) $(0.42) $(0.89) $(0.98)Weighted average common stock outstanding, basic and diluted 77,819,658 71,530,180 75,567,851 70,897,320 Terns Pharmaceuticals, Inc. Selected Balance Sheet Data (Unaudited; in thousands) September 30, 2024 December 31, 2023Cash, cash equivalents and marketable securities $372,777 $263,440 Total assets 378,233 268,517 Total liabilities 13,763 13,150 Total stockholders’ equity 364,470 255,367 About Terns Pharmaceuticals Terns Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology and obesity. Terns’ pipeline contains three clinical stage development programs including an allosteric BCR-ABL inhibitor, a small-molecule GLP-1 receptor agonist, a THR-β agonist, and a preclinical GIPR modulator discovery effort, prioritizing a GIPR antagonist nomination candidate. For more information, please visit: www.ternspharma.com. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements about the Company within the meaning of the federal securities laws, including those related to expectations, timing and potential results of the clinical trials and other development activities of the Company and its partners; the potential indications to be targeted by the Company with its small-molecule product candidates; the therapeutic potential of the Company’s small-molecule product candidates; the potential for the mechanisms of action of the Company’s product candidates to be therapeutic targets for their targeted indications; the potential utility and progress of the Company’s product candidates in their targeted indications, including the clinical utility of the data from and the endpoints used in the Company’s clinical trials; the Company’s clinical development plans and activities, including the results of any interactions with regulatory authorities on its programs; the Company’s expectations regarding the profile of its product candidates, including efficacy, tolerability, safety, metabolic stability and pharmacokinetic profile and potential differentiation as compared to other products or product candidates; the Company’s plans for and ability to continue to execute on its current development strategy, including potential combinations involving multiple product candidates; the Company’s plans and expectations around the addition of key personnel; and the Company’s expectations with regard to its cash runway and sufficiency of its cash resources. All statements other than statements of historical facts contained in this press release, including statements regarding the Company’s strategy, future financial condition, future operations, future trial results, projected costs, prospects, plans, objectives of management and expected market growth, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “target,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. The Company has based these forward-looking statements largely on its current expectations, estimates, forecasts and projections about future events and financial trends that it believes may affect its financial condition, results of operations, business strategy and financial needs. In light of the significant uncertainties in these forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. These statements are subject to risks and uncertainties that could cause the actual results and the implementation of the Company’s plans to vary materially, including the risks associated with the initiation, cost, timing, progress, results and utility of the Company’s current and future research and development activities and preclinical studies and clinical trials. These risks are not exhaustive. For a detailed discussion of the risk factors that could affect the Company’s actual results, please refer to the risk factors identified in the Company’s SEC reports, including but not limited to its Annual Report on Form 10-K for the year ended December 31, 2023. Except as required by law, the Company undertakes no obligation to update publicly any forward-looking statements for any reason. Contacts for Terns InvestorsJustin Nginvestors@ternspharma.com MediaJenna UrbanBerry & Company Public Relationsmedia@ternspharma.com

临床1期财报临床结果高管变更

2024-10-10

·BioPharmaDive

Drugmakers are racing to find the next Wegovy. These obesity trials are ones to watch.

Within the pharmaceutical industry, a multibillion-dollar race is underway to top Novo Nordisks and Eli Lillys in-demand obesity drugs.Dozens of companies, large and small, have set out to test experimental medicines they claim could be more potent, convenient or have fewer side effects than Novos Wegovy and Lillys Zepbound. But those two companies are already hard at work with successors of their own.The next six months figure to be an important preview. Data are expected for a number of drugs that are already, or are shaping up to be, contenders in this high-stakes competition. The readouts will be closely watched, as they will set expectations for how the obesity drug market currently a duopoly between Lilly and Novo will look in the future. Heres what to expect:Zepbound versus WegovyHead-to-head trials always carry high risk. Any company that sponsors one is doing so with the knowledge testing could reveal its drug is equivalent to a competitor or, worse, less effective.With Zepbound, Eli Lilly appears to believe its a risk worth taking. In a trial called SURMOUNT-5, Lilly enrolled 700 people in an attempt to prove Zepbound is better than Wegovy at reducing the body mass of people with obesity or who are overweight, and have another weight-related complication like heart disease or high blood pressure.It expects to have results by the end of the year, and the findings could impact physician and patient perception of which drug offers greater weight loss benefits..So far, Zepbound has seemed superior, as testing showed treatment helped people with obesity lose up to 21% of their body weight. The comparative figure for Wegovy was 16% in the Phase 3 trials Novo used to gain Food and Drug Administration approval. Based on this, Leerink Partners analyst David Risinger expects Zepbound to show a statistically significant advantage in the head-to-head trial.A resoundingly positive outcome could help push Lilly past $1 trillion in market valuation, a milestone that would be a first among pharmaceutical firms. Lilly is currently worth nearly $900 billion.Yet Lilly has yet to prove Zepbound can prevent cardiovascular complications in people with obesity or who are overweight and already have heart disease, as Novo has with Wegovy. That study result helped Novo gain limited Medicare coverage for people with existing heart disease. Lilly has an outcomes trial called SURPASS-CVOT underway, but doesnt expect to have data until next year.Novos dual agonistWegovy works by stimulating a metabolic hormone called GLP-1, while Zepbound targets GLP-1 and a second one called GIP. The biology behind the dueling approaches is still being sorted, but Zepbounds dual agonism has set a model for others to follow, including Novo.The Danish company is now in late-stage testing with a dual-acting experimental drug it calls cagrisema. The drug combines semaglutide, the active ingredient in Wegovy, with another compound that mimics a metabolic hormone called amylin.Cagrisemas Phase 3 trial, called REDEFINE1, is due to wrap up and generate data in the fourth quarter. The results could help Novo fight off Lillys commercial challenge should SURMOUNT-5 favor Zepbound over Wegovy.REDEFINE1 tests cagrisema against a placebo and Wegovy, measuring weight loss over 68 weeks in about 3,400 people. Cagrisemas performance against Wegovy should give analysts a sense of how well it might also measure up against Zepbound, once the SURMOUNT-5 data are available.Novo is also testing cagrisema directly against Zepbound, but that trial isnt due to generate data for another year.Amgens contenderAmgen isnt known for cardiometabolic drugs, but it has one, called maridebart cafraglutide or maritide, thats among the most closely-watched obesity medicines not owned by either Lilly or Novo.Maritide targets the same two gut hormones, GLP-1 and GIP, that Zepbound does. But, somewhat controversially, it is designed to inhibit rather than stimulate GIP. It is also a monthly shot, compared with the weekly injections used for Wegovy and Zepbound.Phase 2 results for maritide are due by the end of the year. Enthusiasm for the experimental drugs potential has driven Amgens shares higher this year sometimes dramatically so. Phase 1 data Amgen disclosed in February suggested it might drive the most weight loss among tested drugs over 12 weeks, according to Stifel analysts.The Phase 2 trial enrolled nearly 600 people with obesity, some of whom also have diabetes, and randomized them to receive one of several doses of maritide or a placebo. Researchers will measure weight loss over 52 weeks.An obesity pillNovo has advanced an oral version of Wegovy and Lilly has pushed its pill oforgliproninto Phase 3 trials. But there are many rivals staking their competitive future on the idea that people with obesity will prefer a pill over a shot. Roche is one such company, having acquired Carmot Therapeutics for $2.7 billion in late 2023 to gain access to three obesity drugs.A Phase 1 dosing trial of the GLP-1 pill CT-996 is due to wrap up by November, which will give Roche and its investors an idea of the drugs biological activity, safety and weight loss. Roche already reported data from earlier stages of the trial, which tested single and increasing doses in trial volunteers who are overweight or have obesity. The third part will test the pill in 60 people who have diabetes in addition to obesity or being overweight.Roche has already said CT-996 will advance into Phase 2 clinical development based on the Phase 1 data. Its already touting the drugs best-in-class potential, although Phase 2 data will be a better test of that claim. Others are already in Phase 2, including Pfizer with its drug danuglipron and Structure Therapeutics with GSBR-1290. They could soon be joined by Terns Pharmaceuticals TERN-601 and Viking Therapeuticsoral version of VK2735.Preserving muscle massThe rapid weight loss stimulated by GLP-1 agonists melts away muscle as well as fat. That worries some experts, who note how people who discontinue treatment tend to regain weight in the form of fat. Muscle cells also have a higher resting metabolic rate, which results in higher caloric burn.In response, some drugmakers are exploring ways to preserve lean muscle mass. An early test could come in the form of results for Verus enobosarm, a type of drug that stimulates muscle-building hormones. Previously sold under the name Ostarine, it has been tested clinically in people with cancer whose muscles have shrunk, as well as those with muscular dystrophy.In obesity, a Phase 2 test of enobosarm together with Wegovy is underway in people 60 and over who are overweight or have obesity and have lost muscle mass. The trial will measure how much trial volunteers muscle mass changes over 16 weeks, and will compare results in people who receive the two drugs to those who were given only Wegovy. Another endpoint will assess physical function by evaluating how participants climb stairs.Veru expects results by the end of the year. The data could help analysts parse how important lean mass might be in future obesity treatment.A new drug targetOutside of targeting GLP-1, GIP, amylin and other gut hormones, there are a range of other treatment approaches under evaluation. One involves blocking a cannabinoid receptor called CB1 that is known for regulating an appetite-modulating hormone called leptin. CB1 is known to have effects on other biological functions such as inflammation, too.So far, theres been at least one disappointing data point on CB1 inhibition. Phase 2 data for a Novo drug called monlunabant didnt meet expectations for weight loss, leading Novo to state that further work is needed to determine the optimal dosing.The next shot for CB1 may be Skye Biosciences nimacimab, which is due to have interim Phase 2 results by mid-2025. The trial, called CBEYOND, tests nimacimab against placebo, as well as a combination of Wegovy and nimacimab against Wegovy alone. The study will measure weight loss over 26 weeks. Enrolling 120 volunteers, the study should be large enough to detect at least an 8% difference between the experimental drug and placebo, according to the trials plan.Skye shares fell by more than 40% the same day Novo reported its data for monlunabant. '

临床2期临床3期并购临床1期临床结果

2024-09-17

·BioSpace

Obesity Pill Races Heats Up as Novo, Roche and Terns Share Data

iStock, master1305 The release of early-stage data on three oral weight loss drug candidates hints at which companies have the strongest hand, but the comparisons are rife with confounding variables, leaving analysts unsure about where to place their bets. Novo Nordisk, Roche and Terns Pharmaceuticals used last week’s European Association for the Study of Diabetes annual meeting to present new data on their oral obesity candidates. After four weeks of dosing, the placebo-adjusted weight loss figures were 4% for Novo’s amycretin, 4.9% for Terns’ TERN-601 and 6.1% for Roche’s CT-996. Slotting the three candidates into a ranking of oral obesity drug candidates by placebo-adjusted weight loss after four weeks enables an early attempt to order the molecules and rival drugs by efficacy. In earlier data drops, the comparable figures were 3.2% for Viking Therapeutics’ VK2735, 3.9% for Eli Lilly’s orforglipron, 4.9% for Structure Therapeutics’ GSBR-1290 and 5.2% for Pfizer’s danuglipron. Based on the figures, Roche and Pfizer hold the top two spots, with Structure and Terns tied for third. However, it is unclear whether the figures reflect differences between the molecules or the trial designs, analysts warned, noting that these early cross-trial assessments always introduce factors that can confound attempts to compare efficacy. Roche’s Tolerability Data Disappoint While Roche saw the most weight loss, Jefferies analysts said in a note to investors that the competitive result “appears driven by rapid titration.” The fast speed at which Roche increased the doses may explain both the strong efficacy and high rates of adverse events seen in the study. Taken at face value, the data suggest CT-996 is more efficacious and less tolerable than the competition. Yet, the Jefferies analysts said the molecule’s “true competitive profile” will not be known until Roche runs larger Phase II trials, which could dial down efficacy and side effects using lower starting doses and smaller or less frequent dose increases. For now, the tolerability data are overshadowing the promising efficacy, with Roche reporting rates of nausea, diarrhea and vomiting of 83.3%, 50.0% and 33.3%, respectively, even in the less rapidly titrated cohort. BMO analysts gave their take on the figures and data on Roche’s injectable obesity candidate in a note to investors. “While Ph 1 results slightly underperformed expectations this week on tolerability, Roche is likely to remain a relevant player in obesity development, even if they are a step behind leaders like Lilly and Novo,” the analysts said. Novo Faces Manufacturing Questions Truist analysts said in a note to investors that Novo’s tolerability update on its oral amycretin “was a bit underwhelming” but that reflected the lack of positive differentiation rather than a downside versus other oral GLP-1 drugs. In addition to GLP-1, the molecule engages amylin, enabling it to act on glucose control and appetite via a different pathway than rival drug candidates, BMO analysts described. “Amylin was one of the hottest topics of the conference, with a number of presenters highlighting the importance of optionality when you are looking to treat [a] heterogeneous disease like obesity,” BMO analysts wrote. “The target offers benefits separate from and synergistic to what we have seen from the GLP-1 class.” The analysts said the molecule’s efficacy is potentially best in class but added that “given amycretin is a peptide, we would like to hear more from Novo on manufacturing.” Jefferies analysts expanded on why manufacturing could be a problem for Novo. “Based on conservative Phase I titration info, even our $5bn amycretin WW peak sales may require >30 tonnes of API p.a. if the oral route is prioritized, suggesting reformulation for greater bioavailability through tweaking SNAC technology is critical,” the analysts said. Terns’ Novel Approach Catches Attention Terns’ results were in line with the Jefferies analysts’ bull case, with the company reporting weight loss at the upper end of the spectrum achieved by rivals. Gastrointestinal side effects were common, with 88% of people reporting nausea on one dose, but more than 85% of treatment-emergent adverse events were mild. The Jefferies analysts spotted details that could differentiate Terns. “Here’s what surprised us – we think there’s a possibility [Terns] could have a dose that could thread the needle in larger trial by showing tolerability that could approach [Lilly’s orforglipron] (but too soon to say) despite a less than ideal PK/PD pro competitive 10-15% 52 week [weight loss],” the analysts said. “Interestingly, [Terns] is taking an approach we have not seen with other oral GLP-1s so far.” The analysts said the high plasma protein binding, low solubility and high gut permeability of Terns’ drug candidate means the “oral-GLP-1 is accumulating in the gut in a manner that meaningfully extends its effective exposure, pretty similar to a long-acting oral.” The pro allow Terns to give relatively high doses to maximize weight loss without causing intolerable side effects, the analysts said. However, the downsides are that the approach requires people to take lots of tablets and high doses with potential variability, the analysts said. Like its rivals, Terns needs to generate Phase II data to start to clear up the questions about its candidate.

临床1期临床结果临床2期

100 项与 TERN-601 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
肥胖	临床1期	美国	Terns Pharmaceuticals, Inc.	2023-11-02
非酒精性脂肪性肝炎	临床前	美国	Terns Pharmaceuticals, Inc.	-

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Company_Website 人工标引	临床1期	肥胖	-	TERN-601 240 mg	齋顧齋鏇構襯構選窪夢(鑰夢鹽襯範蓋壓積觸鑰) = 積鹹蓋齋積製膚繭憲網積願壓齋衊襯製艱壓積 (襯膚選鏇鑰繭窪願積衊 ) 更多	积极	2024-09-09
				TERN-601 500 mg	齋顧齋鏇構襯構選窪夢(鑰夢鹽襯範蓋壓積觸鑰) = 襯鹽顧餘鏇鑰鑰獵壓襯積願壓齋衊襯製艱壓積 (襯膚選鏇鑰繭窪願積衊 ) 更多
ADA2020	N/A	-	-	GL0001	艱艱構網獵獵願衊膚淵(齋窪醖齋鏇鬱積淵遞觸) = 範蓋窪窪鹹廠齋齋構鬱糧餘鑰夢夢繭糧製願醖 (範壓夢鹹鹹壓醖觸襯築 ) 更多	-	2020-06-01
				GL0028	艱艱構網獵獵願衊膚淵(齋窪醖齋鏇鬱積淵遞觸) = 憲製糧壓淵膚繭簾憲選糧餘鑰夢夢繭糧製願醖 (範壓夢鹹鹹壓醖觸襯築 ) 更多
EASD2019	N/A	-	-	GLP-1R agonist 10 nM	蓋範鏇積簾淵積壓蓋範(遞築網憲積鑰衊遞醖廠) = 鹽窪憲獵選願網廠糧構齋鹽憲蓋簾繭願願夢憲 (餘鏇願膚顧範襯憲糧獵 )	积极	2019-09-17
				GLP-1R agonist 100 nM	蓋範鏇積簾淵積壓蓋範(遞築網憲積鑰衊遞醖廠) = 網積夢窪製齋顧夢艱蓋齋鹽憲蓋簾繭願願夢憲 (餘鏇願膚顧範襯憲糧獵 )