Pharma Friday – ENDO 2026 Edition – June 19, 2026

An Endocrine News roundup of the week’s pharmaceutical news, breakthroughs, and general information. *

Crinetics Presents Full Results From Phase 2 Trial of Atumelnant in CAH at ENDO 2026

On June 14, Crinetics Pharmaceuticals, Inc.  presented data from the open-label, Phase 2 congenital adrenal hyperplasia (CAH) adult study of investigational atumelnant, a novel, once-daily oral adrenocorticotropic hormone (ACTH) receptor antagonist candidate being developed for the treatment of classic CAH and ACTH-dependent Cushing’s syndrome.

The findings were included in an oral presentation titled “Once Daily Atumelnant (CRN04894) Enables Lowering of Glucocorticoid Doses with Sustained Androgen Reduction in Adults with Congenital Adrenal Hyperplasia” at ENDO 2026.

“Atumelnant is designed to block the effect of excess ACTH, the fundamental driver of symptoms and complications of CAH and ADCS,” said Alan Krasner, MD, Chief Endocrinologist, Crinetics. “Based on promising results from phase 2 clinical trials presented today, we are advancing atumelnant into late phase clinical development. The data suggest atumelnant could represent a uniquely effective and simple to use oral therapy for many patients who need new options.”

“It’s exciting to see that glucocorticoid dose reduction did not impact the atumelnant-induced decline in androstenedione in adults with classic CAH who participated in this Phase 2 trial,” said Umasuthan Srirangalingam, MD, consultant physician in endocrinology and diabetes at University College London Hospitals NHS Foundation Trust and TouCAHn Investigator. “We are looking forward to learning more about the full potential of atumelnant in the treatment of CAH from adult and pediatric Phase 3 trials that are already underway.”

At ENDO 2026, findings from Cohort 4 of the Phase 2 CAH trial were presented for the first time, including the percent change from baseline in morning serum A4, 11-OHA4, and 11-KT with GC reduction. Participants in Cohort 4 received dosing of 80 mg once daily in the morning. Beginning at week 2 of treatment, each participant’s previous GC dose was reduced stepwise by 5-10 mg HC equivalents, independent of A4 measurement, to target <11 mg/m²/day HC equivalents.

Phase 2 CAH Cohort 4 Results

• At week 12, the mean percentage change from baseline in A4 morning serum levels in Cohort 4 was -67%.
• Seven out of eight participants (88%) who completed 12 weeks of treatment achieved a physiologic daily dose of GC.
• Reductions in pre-GC serum 11-OHA4 and 11-KT were rapid and sustained, with mean change from baseline of -64% and -56% at week 12, respectively.
• Morning dosing of atumelnant resulted in similar androgen reductions as seen in previous cohorts with evening administration.

Atumelnant was generally well tolerated with no treatment-related severe or serious adverse events to date, irrespective of disease severity or dose level.

Initial findings from the adult Phase 2 trial in CAH, including A4 reduction levels compared to baseline for cohorts 1-3, in which participants did not change previous GC doses, were presented at ENDO 2025.

Topline results from Cohort 4 were announced in January 2026.

Previously Reported A4 Reductions for Cohorts 1-3 (no GC reduction)

New Phase 1b/2a ADCS Trial Results

Data presented at ENDO 2026 include findings from a cohort dosed with atumelnant 40 mg once daily (n=6). Findings include:

• Atumelnant rapidly lowered early morning serum cortisol in all participants.
• Atumelnant also rapidly lowered UFC. At the end of the 10-day dosing period, UFC remained ≤ upper limit of normal (ULN) in 3/6 participants.
• Most AEs were mild to moderate and consistent with symptoms of adrenal insufficiency.  Most improved with initiation of GC replacement.

Atumelnant ENDO 2026 presentations can be found at: https://crinetics.com/news-events/endo-2026/

About Atumelnant

Atumelnant, Crinetics’ second investigational compound, is the first once-daily, oral adrenocorticotropic hormone (ACTH) receptor antagonist that acts selectively at the melanocortin type 2 receptor (MC2R) on the adrenal gland. Diseases associated with excess ACTH can have significant impact on physical and mental health. Atumelnant has exhibited strong binding affinity for MC2R in preclinical models and has demonstrated suppression of adrenally derived glucocorticoids and androgens that are under the control of ACTH. Data from a 12-week Phase 2 study demonstrated compelling treatment benefits of atumelnant, evidenced by the rapid, substantial and sustained statistically significant reductions in key CAH disease related biomarkers, including androstenedione and 17-hydroxyprogesterone, in a diverse population. Atumelnant is in development for congenital adrenal hyperplasia and ACTH-dependent Cushing’s syndrome, with the Phase 3 CALM-CAH trial and a Phase 1/2b trial in ADCS currently enrolling patients.

About the Phase 2 TouCAHn Trial (CAH)

The TouCAHn trial is an open-label, global, Phase 2 study designed to evaluate the efficacy, safety, and pharmacokinetics of atumelnant when administered for 12 weeks in people with classic CAH (21-hydroxylase deficiency). A total of 38 participants were enrolled, with a median A4 of 980.8 (range=116-2755) ng/dL were enrolled in four cohorts: (40 mg, n=11; 80 mg, n=11; 120 mg, n=6; 80 mg morning dosing with GC reduction, n=10).

Primary endpoints included change from baseline in morning serum androstenedione (A4) levels and incidence of treatment-emergent adverse events. Percent change-from-baseline in GC daily dose was an exploratory endpoint for Cohort 4.

About the Phase 1b/2a Study in ACTH-dependent Cushing’s Syndrome

The Phase 1b/2a, is the first-in-disease, open-label, multiple-ascending dose exploratory study to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamic biomarker responses associated with atumelnant over a 10-day inpatient treatment period in participants with ACTH-dependent Cushing’s syndrome.

The study is being conducted in collaboration with the National Institutes of Health and led by Dr. Lynnette Nieman. Participants received oral atumelnant once daily for 10 days, followed by monitoring during four wash-out days.

Crinetics Presents Long-Term Data at ENDO 2026 Confirming PALSONIFY^TM (paltusotine) Provides Durable, Consistent Acromegaly Control

Also on June 14, Crinetics Pharmaceuticals, Inc. announced new long-term data from its clinical development program evaluating novel PALSONIFY^TM (paltusotine) in acromegaly during an oral presentation at ENDO 2026.

Notably, pooled data from the open-label extension (OLE) trials of PATHFNDR-1 and PATHFNDR-2 show that after two years of treatment, PALSONIFY was effective and well-tolerated in patients who were switched from standard-of-care monthly injectable somatostatin receptor ligands (SRLs) and those who were medically untreated, respectively, when oral, once-daily PALSONIFY was initiated.

“To assess acromegaly disease control while on medication, endocrinologists carefully monitor control of IGF-1 levels, control of acromegaly symptoms, and stabilization of pituitary tumors,” said Alan Krasner, MD, chief endocrinologist, Crinetics. “At this year’s ENDO meeting, long-term safety and efficacy data from the PATHFNDR OLE trials will be presented. These studies indicate that Palsonify is well tolerated and maintains control of all three aspects of disease control with long-term follow-up. Since its launch late last year, we are learning that Palsonify is already making a meaningful difference in the lives of many people with acromegaly, and we hope these data will be helpful for patients and for their health care providers.”

Pooled OLE Efficacy and Safety Results

PATHFNDR-1 Data

The PATHFNDR-1 Phase 3 trial enrolled adults with acromegaly who were biochemically controlled on monthly injectable SRLs. Following a 36-week randomized, placebo-controlled period, 53 of 57 participants (93%) entered the ongoing single-arm open-label extension (OLE) trial.

Baseline mean IGF-1 levels for OLE participants (n=53) was 0.91x Upper Limit of Normal (ULN). These levels remained stable at both 48 weeks (n=50) and 96 weeks (n=47) of the study: 0.82x ULN and 0.81, respectively. Symptoms associated with acromegaly, as measured by the Acromegaly Symptom Diary (ASD), remained stable from baseline at assessed timepoints. Additionally, pituitary tumor volumes were reported as stable in all patients at week 48, relative to OLE baseline.

PATHFNDR-2 Data

The PATHFNDR-2 trial evaluated once-daily oral PALSONIFY in adults with biochemically uncontrolled acromegaly (baseline IGF-1 > 1.3 × ULN). After a 24-week randomized controlled (RC period, 103 of 106 completers (97.2%) entered the ongoing OLE, along with 11 additional patients who were eligible for the RC phase but enrolled directly into the OLE.

Baseline mean IGF-1 levels for OLE participants (n=114) was 1.64×ULN. These levels decreased from baseline at both 48 weeks (n=98) and 72 weeks (n=78) of the study: 1.06×ULN and 0.96×ULN, respectively.

Relative to OLE baseline, pituitary tumor volume was reduced by >20% in 7 of 83 PATHFNDR-2 patients with available MRI scans at OLE Week 24. Tumor volume was reported as stable in the other 76 participants.

In both OLEs, median ASD scores were stable at the timepoints assessed. Symptoms associated with acromegaly, as measured by the Acromegaly Symptom Diary (ASD), remained stable from baseline at assessed timepoints.

No new safety signals were found. In the pooled OLE population (n=167), the most common adverse events (incidence>10%) were diarrhea (15.6%), arthralgia (11.4%), headache (11.4%), and urinary tract infection (10.2%). Four patients (2.4%) discontinued from an OLE due to adverse events as of this analysis.

These results were included in an oral presentation at ENDO 2026 titled “Efficacy and Safety of Once-Daily Oral Paltusotine in Patients with Acromegaly: Up to 2 Years in the PATHFNDR-1 and PATHFNDR-2 Open-Label Extension Studies.”

Additionally, an analysis was presented at ENDO 2026 that evaluated the safety and efficacy of PALSONIFY in combination with oral cabergoline in patients with acromegaly who have been followed for up to four years in ACROBAT Advance, an ongoing, single-arm, open-label extension phase 2 study. IGF-I levels on paltusotine monotherapy were similar to parent study baseline values (on injected SRL), but for those in whom IGF-1 had not yet normalized, it further improved when oral cabergoline was added. Combination therapy was well tolerated.

Crinetics’ ENDO 2026 presentations can be found at: https://crinetics.com/news-events/endo-2026/

Marea Therapeutics Presented Data Supporting Potential Best-in-Disease Profile Acromegaly Treatment at ENDO 2026

On June 15, Marea Therapeutics, Inc., highlighted data from its first-in-human Phase 1 study of MAR002 at ENDO 2026 in Chicago, Ill. MAR002 is a first-in-class allosteric monoclonal antibody targeting the growth hormone receptor (GHR).

Marea Therapeutics, Inc., is a clinical-stage biotechnology company harnessing the latest advances in human genetics to develop first-in-class, next-generation medicines for cardioendocrine diseases,

Data from the Phase 1 study support a potential best-in-disease profile of MAR002 across safety, tolerability, pharmacodynamic effect, and dosing convenience – with deep, durable IGF-1 suppression that may enable dosing as infrequently as once every two weeks, compared to the daily subcutaneous injections required by the current standard of care.

“The Phase 1 data presented at ENDO provide compelling proof-of-mechanism for MAR002 and strengthen our confidence as we advance into a Phase 2/3 study in patients with acromegaly expected to begin in the coming weeks,” said Rebecca Juliano, PhD, chief development officer of Marea Therapeutics. “MAR002 demonstrated deep and durable suppression of IGF-1, a validated biomarker and regulatory endpoint in acromegaly, while exhibiting pharmacokinetic properties that may support convenient dosing as infrequently as every two weeks. By directly blocking growth hormone signaling at the receptor level, MAR002 has the potential to deliver meaningful biochemical control for a broad population of patients and establish a new standard of care in acromegaly.”

“Acromegaly remains a disorder of significant unmet need, with fewer than 35% of patients achieving optimal disease control on first-line medical therapy,” said Shlomo Melmed M.D., Distinguished Professor and Dean at Cedars-Sinai. “The depth of initial IGF-1 suppression reported with MAR002 of up to 64% is particularly notable, as it appears to exceed levels seen with previously reported therapies in acromegaly. Based on these early findings, and if proven safe, MAR002 has the potential to become a significant advancement in both efficacy and treatment convenience for patients with acromegaly.”

Presentation Highlights

• The first-in-human, randomized, blinded, parallel-group, placebo-controlled Phase 1 study enrolled healthy adult male volunteers and single ascending doses of MAR002 demonstrated a favorable safety and tolerability profile, with no serious adverse events or dose-limiting toxicities.
• Treatment with MAR002 resulted in robust and durable dose-dependent reductions in circulating insulin-like growth factor-1 (IGF-1) with up to 64% peak suppression.
• Favorable pharmacokinetic (PK) profile support bi-weekly to monthly dosing.

Recordati Rare Diseases, Inc., Presents Data Analyses at ENDO 2026

On June 15, Recordati Rare Diseases, Inc., announced new data analyses at ENDO 2026 from four poster presentations featuring the company’s endocrinology portfolio.

The data presented include outcomes with ISTURISA® (osilodrostat) across the LINC clinical program, drawing on pooled clinical trial and real-world analyses to assess patient-reported quality of life, biochemical control, and clinical outcomes across a range of Cushing’s syndrome populations, including those with milder disease, as well as ongoing evaluation in studies such as LINC CARE. 

“Engagement with the endocrinology community at ENDO 2026 highlighted the importance of continuing to build robust, long-term evidence for patients living with Cushing’s syndrome to support long-term management,” commented Milan Zdravkovic, executive vice president, head of R&D and CMO, Recordati. “Analyses from the LINC programme support previously established sustained efficacy and further assess meaningful improvements in quality of life with ISTURISA®, reinforcing its role as an important long-term treatment option.”

Melissa Koomey, president and General Manager North America, Recordati Rare Diseases, added, “The response to our data presentations at ENDO 2026 highlights the growing commitment across the US endocrinology community to advancing care for people living with rare endocrine diseases. We are encouraged by the strong interest in the expanding body of evidence supporting ISTURISA® and remain committed to working alongside clinicians, researchers, and patient communities to help address ongoing unmet needs and improve patient outcomes in Cushing’s syndrome.” 

Key Data Presentations at ENDO 2026

Martin Reincke, MD, LMU Hospital, Ludwig-Maximilians-Universität, introduced the LINC CARE Phase IV study evaluating the efficacy and safety of osilodrostat in patients with hypertension caused by hypercortisolemia due to Cushing’s syndrome despite medication.

• Poster number: MON-105
• This study addresses an important unmet need in Cushing’s syndrome patients with mild elevations in cortisol, a population often underrepresented in research despite substantial cardiometabolic burden, including high baseline rates of hypertension and dysglycemia observed in prior LINC 3 and LINC 4 analyses

Antoine Tabarin, MD, from CHU de Bordeaux and Centre de Référence des Maladies Rares de la Surrénale, presented promising results from LINC 7, a retrospective observational study, which assessed the safety and effectiveness of osilodrostat in adrenal and ectopic Cushing’s syndrome.

• Poster number: SAT-036
• In this secondary analysis of the LINC 7 retrospective observational study, osilodrostat reduced cortisol levels across all Cushing’s syndrome etiologies and severities, including mild benign adrenal Cushing’s syndrome, mild malignant Cushing’s syndrome, and moderate-severe Cushing’s syndrome

Eliza B. Geer, MD, from Memorial Sloan Kettering Cancer Center, presented an ad hoc analysis of the ongoing LINC 6 study which is assessing the long-term safety and efficacy of osilodrostat in patients with endogenous Cushing’s syndrome during 3 years of routine clinical practice.

• Poster number: SAT-013
• Improvements in quality of life were observed in patients with Cushing’s syndrome during osilodrostat treatment. Biochemical and clinical parameters improved or remained stable over time in most patients

Beverly Biller, MD, from Massachusetts General Hospital, presented an analysis of patient reported outcomes from the Phase III LINC 3 and LINC 4 studies.

• Poster number: MON-026
• Patients treated with osilodrostat in the pooled analysis showed improved Health-Related Quality of Life (HRQoL) across all reported HRQoL instruments, with sustained, clinically meaningful improvements observed to week 72. Improvements were consistent across the disease-specific CushingQoL and generic EQ-5D-5L and BDI-II questionnaires. The greatest improvements in HRQoL occurred in items/domains with the greatest burden at baseline. 

Ethyreal Bio Presents First Preclinical Data on ETHY-001 Demonstrating Complete Blockade of Autoantibody Activation of TSHR and Differentiated Activity in TED

Ethyreal Bio, a biotechnology company developing precision therapies for thyroid diseases with high unmet need, today reported preclinical data for its lead program, ETHY-001, in an oral presentation at ENDO 2026 on June 15.

ETHY-001 is an internally discovered, half-life-extended monoclonal antibody designed to block autoantibody-mediated activation of the thyroid stimulating hormone receptor (TSHR), the shared pathogenic driver of Graves’ disease (GD) and thyroid eye disease (TED).

“The data presented today underscore the promise of ETHY-001 for the treatment of TED and GD,” said Niranjan Kameswaran, PhD, chief executive officer of Ethyreal Bio. “The depth and consistency of signaling blockade across all tested patient sera samples, combined with its differentiated activity compared to IGF-1R antagonism in TED models, reinforce our conviction in ETHY-001’s product profile. We believe that ETHY-001’s unique combination of potent receptor blockade, subcutaneous administration, and extended half-life supports a best-in-class, convenient, single-agent approach for both conditions. We are excited to advance ETHY-001 into the clinic this year.”

Key preclinical results for ETHY-001 shared in the oral presentation include:

• Potent binding with high specificity for TSHR. ETHY-001 binds TSHR with sub-nanomolar monovalent affinity and no off-target binding in a membrane protein array of over 5,000 membrane proteins.
• Complete, consistent, and broad blockade of TSHR activation. ETHY-001 completely blocked autoantibody-driven TSHR activation elicited from all patient samples tested to date.
• Differentiated activity versus anti-IGF-1R in TED patient-derived orbital fibroblasts. In primary TED patient-derived orbital fibroblast cultures stimulated by M22, a potent stimulating antibody of TSHR, ETHY-001 produced complete inhibition of both HA and IL-6 secretion. An IGF-1R antagonist comparator inhibited HA secretion but not IL-6 secretion. These observations demonstrate ETHY-001’s potential for more robust inhibition of pathogenic signaling in comparison to anti-IGF-1R in TED.

Together, these data support the advancement of ETHY-001 into clinical development for TED and GD, with potential to be a single, best-in-class, mechanism-driven therapy. Ethyreal plans to initiate a first-in-human trial in the second half of 2026.

Rezolute Highlights Results Presented from Natural History Outcomes Studies and its Ersodetug Clinical Program in Hyperinsulinism at ENDO 2026

On June 17, Rezolute, Inc., a late-stage ultra-rare disease company focused on treating refractory hypoglycemia caused by a congenital or any acquired form of hyperinsulinism (HI), highlighted four data presentations delivered at ENDO 2026.

Two poster presentations highlighted results from systematic analyses of the natural history and adverse neurologic and health-economic outcomes resulting from congenital HI, using a meta-analysis of the literature as well as a claims-based approach to quantifying congenital HI complications, respectively. This is an important step toward consolidating and quantifying the disease-impact and informing future health economics and outcomes research that will facilitate the development and potential future launch of the company’s therapy, ersodetug, in this indication. A third poster presentation highlighted favorable outcomes from a case series report of 9 patients with refractory hypoglycemia due to malignant insulinoma and non-islet cell tumors (tumor HI), demonstrating that 75% of the patients receiving IV dextrose/total parenteral nutrition (TPN) in the EAP achieved a complete discontinuation of IV dextrose/TPN.

In an oral presentation, Huseyin Demirbilek, MD, professor, Department of Pediatric Endocrinology, Hacettepe University Faculty of Medicine, Ankara, Turkey, and Principal Investigator of the Phase 3 sunRIZE study of ersodetug in congenital HI, reviewed previously reported sunRIZE results.

“We were pleased to have the opportunity to present at ENDO and to continue showcasing progress across our two late-stage programs in congenital and tumor HI,” said Brian Roberts, MD, chief medical officer of Rezolute. “Deeper analyses of the sunRIZE data demonstrate the meaningful therapeutic benefit of ersodetug, further supported by the positive outcomes observed in both our EAP and recently announced interim and preliminary Phase 3 upLIFT study observations in tumor HI patients. Additionally, the natural history outcomes studies further underscore the significant clinical outcomes impacts of this disease, and the urgent need for improved treatment options.”

Each of the company’s full data presentations from ENDO can be found on the Publications and Presentations page of the Rezolute website here.

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