Scholar Rock Announces FDA Clearance of IND Application to Initiate Phase 2 Proof-of-Concept Trial with Apitegromab to Treat Obesity

• Randomized Phase 2 proof-of-concept trial with apitegromab in patients with obesity on GLP-1 therapies on track to initiate mid-2024
• Study aims to show the importance of selective myostatin inhibition in preservation of lean muscle mass as part of healthy, safe weight loss management
• Scholar Rock is also developing SRK-439, a novel investigational selective myostatin inhibitor, optimized for the treatment of obesity

CAMBRIDGE, Mass.--Jan. 23, 2024-- Scholar Rock (NASDAQ: SRRK) (the Company), a late-stage biopharmaceutical company focused on advancing innovative treatments for spinal muscular atrophy (SMA), cardiometabolic disorders, and other serious diseases where protein growth factors play a fundamental role, today announced that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for its Phase 2 proof-of-concept trial of apitegromab to treat obesity in patients taking a GLP-1 receptor agonist (GLP-1 RA).

The Phase 2 trial is a randomized, double-blind, placebo-controlled, multi-center study to evaluate the effect of apitegromab, a highly selective myostatin inhibitor, to safely preserve lean muscle mass as an adjunctive therapy in overweight and obese adults who are taking a GLP-1 RA. Trial initiation is on track for mid-2024, and data from the apitegromab Phase 2 trial are expected in mid-2025. In parallel, Scholar Rock is developing SRK-439, a novel investigational selective myostatin inhibitor, optimized for the treatment of obesity. The Company plans to file an IND for SRK-439 in 2025.

“The FDA’s acceptance of our IND application to study apitegromab in obesity allows us to assess the effect of our highly selective myostatin inhibitor on preserving lean muscle mass, and safety and tolerability of our approach when combined with a GLP-1 RA. The IND builds on our encouraging apitegromab clinical and safety data to date and allows us to inform the development of our cardiometabolic program with SRK-439, a novel preclinical selective myostatin inhibitor optimized for development in cardiometabolic disorders,” said Jay Backstrom, M.D., MPH, President and Chief Executive Officer of Scholar Rock. “Maintaining lean mass during weight loss is important to overall metabolic health, and we look forward to initiating the Phase 2 proof-of-concept trial in apitegromab to validate our differentiated approach of selectively targeting only the pro- and latent forms of myostatin to retain muscle mass.”... Scholar Rock's Press Release -

Rhythm Pharmaceuticals Announces Completion of Screening for Enrollment in Setmelanotide Phase 3 Hypothalamic Obesity Trial and Additional Updates

-- Phase 3 hypothalamic obesity top-line data expected in 1H2025 --

-- Positive reimbursement decision achieved for IMCIVREE® (setmelanotide) to treat patients with Bardet-Biedl syndrome and POMC/LEPR deficiencies in Spain --

-- IND application for RM-718 accepted by the FDA --

BOSTON, Jan. 04, 2024 -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a global commercial-stage biopharmaceutical company focused on transforming the lives of patients and their families living with rare neuroendocrine diseases, provided a business update and announced it has completed screening for enrollment in the pivotal, Phase 3 clinical trial evaluating setmelanotide in patients with acquired hypothalamic obesity.

Rhythm closed screening and anticipates overenrolling the ongoing phase 3 hypothalamic obesity trial with more than 140 patients consented and going through active screening and baseline assessments. In this trial, patients with acquired hypothalamic obesity aged 4 years or older will be randomized 2:1 to setmelanotide therapy or placebo for a total of 60 weeks, including up to eight weeks for dose titration. The Company expects to obtain top-line study results in H1 2025.

“2023 was a truly transformational year for Rhythm, as we made excellent progress with the execution of our IMCIVREE® (setmelanotide) commercial plan while also advancing important development efforts to expand the number of patients living with hyperphagia and severe obesity that could potentially benefit from this therapy,” said David Meeker, M.D., Chair, President and Chief Executive Officer of Rhythm. “We believe the rapid over enrollment in less than one year and execution of our Phase 3 hypothalamic obesity trial is a strong indicator of the unmet need for an effective therapy for patients who have no approved therapeutic options and the community’s excitement around setmelanotide’s potential to make a meaningful difference in their lives.”... Rhythm Pharmaceuticals' Press Release -

Keros Therapeutics to Develop KER-065 for the Treatment of Obesity

Keros commenced a randomized, double-blind, placebo-controlled, two-part Phase 1 clinical trial to evaluate single and multiple ascending doses of KER-065 in healthy volunteers

Keros expects to report initial data from this Phase 1 clinical trial in the first quarter of 2025

Preclinical data showed potential proof-of-mechanism of KER-065 for the treatment of obesity

Keros believes these preclinical data support developing KER-065 for the treatment of obesity, and Keros plans to initiate a proof-of-concept trial of KER-065 in obese patients following completion of this Phase 1 clinical trial

LEXINGTON, Mass., Jan. 03, 2024 - Keros Therapeutics, Inc. (“Keros” or “we”) (Nasdaq: KROS), a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapeutics to treat a wide range of patients with disorders that are linked to dysfunctional signaling of the transforming growth factor-beta (“TGF-ß”) family of proteins, announced that it plans to develop KER-065, a novel ligand trap designed to bind to and inhibit TGF-ß ligands, including myostatin (GDF8) and activin A, for the treatment of obesity.

“Obesity is a complex and chronic disease associated with numerous comorbidities and a growing prevalence in patients. We believe there is a need for additional treatment options, including one that leads to weight loss without an associated loss of muscle and a potential for frailty. Based on our preclinical data, we believe that KER-065 has the potential to treat obesity without those limitations, by increasing skeletal muscle, reducing fat mass through an increase in energy expenditure, improving insulin sensitivity and improving cardiac function,” said Jasbir S. Seehra, Ph.D., President and Chief Executive Officer of Keros. “To that end, we recently commenced our Phase 1 clinical trial evaluating KER-065 in healthy volunteers and, following its successful completion, plan to initiate a proof-of-concept trial of KER-065 in obese patients.”... Keros Therapeutics' Press Release - 

Resalis Therapeutics Raises €10 Million Series A to Complete First Clinical Trial for RES-010 in Obesity

January 04, 2024- TORINO, Italy- Resalis Therapeutics announced the closing of a €10 million ($11 million) Series A financing round led by Sunstone Life Science Ventures with participation from existing investors including Claris Ventures and angel investors. The proceeds will be used to initiate and complete the first-in-human Phase 1 clinical trial and reach Phase 2 readiness for Resalis’ lead program, RES-010, in obesity. RES-010 is a non-coding RNA-based compound designed to provide a disease-modifying approach in obesity with longer-lasting weight reduction and the ability to extend treatment durability in combination with approved therapeutics, such as GLP-1 receptor agonists. In conjunction with the financing, Claus Andersson, PhD, General Partner of Sunstone Life Science Ventures, will join Resalis’ Board of Directors.

“The successful close of our Series A is an important milestone for Resalis because it will enable us to reach the clinic and to achieve the next significant inflection point with our lead candidate, RES-010. With RES-010 we aim to provide a therapeutic that precisely reduces fat mass in obesity with the potential to extend the durability of existing therapies. We value the trust and support of our new and current investors, and eagerly look forward to this next phase of development,” said Alessandro Toniolo, CEO of Resalis Therapeutics.

“Resalis’ therapeutic approach is based on groundbreaking science that has rapidly led to the development of a lead candidate, now on the cusp of clinical evaluation. Preserving muscle mass is key to provide a sustained and meaningful clinical benefit, and we share the team’s vision that this non-GLP1/GIP therapeutic will significantly improve both effect and tolerability of today’s therapies. This investment underscores our belief in the company’s vision and the transformative potential of its lead candidate to make a meaningful impact for obese patients,” said Claus Andersson, General Partner at Sunstone Life Science Ventures.

Pietro Puglisi, Managing Partner at Claris Ventures and Chairman of the Board at Resalis Therapeutics, added: “In recent years, there has been remarkable progress in the treatment of metabolic disorders. Yet, there persists a critical need for innovative solutions that can both provide orthogonal therapeutic effects and pave the way for combination therapies. I look forward to the continued collaboration with the outstanding Resalis team and welcoming Claus as a new member of the Resalis Board.”

Resalis has a deep understanding of the field of ncRNAs and RNA-targeted therapeutics in human health and metabolic disorders. The company’s lead candidate, RES-010, is an antisense oligonucleotide that targets miR-22, a central player in the regulation of lipid metabolism and energy consumption. In multiple proof-of-concept studies in large and small animal models, RES-010 has shown the potential to provide a safe and longer-lasting therapeutic effect, alone or in combination with approved drugs. Resalis plans to initiate a Phase 1 clinical study evaluating the safety and efficacy of RES-010 in the first half of 2024. RES-010 is patent-protected in the US, Japan and China with patents pending in the EU... Resalis Therapeutics' Press Release [PDF] - 

Lilly's Zepbound (tirzepatide) achieved additional 6.7% weight loss following a 36-week open-label lead-in period, for a total mean weight loss of 26.0% from study entry over 88 weeks

 People who were randomized to placebo following the lead-in period experienced mean weight regain of 14.8% at 88 weeks, indicating Zepbound led to sustained weight loss compared to placebo

Full results from the SURMOUNT-4 study were published in The Journal of the American Medical Association

INDIANAPOLIS, Dec. 11, 2023 -- Detailed results from SURMOUNT-4, which showed Zepbound™ (tirzepatide) injection achieved superior mean percent change in body weight compared to placebo in adults with obesity or overweight with weight-related comorbidities, excluding type 2 diabetes, were published in The Journal of the American Medical Association (JAMA). Zepbound met the primary endpoint of mean percent change in body weight, and all key secondary endpoints for both estimandsi,ii, compared to placebo 52 weeks after randomization.

Study Design

SURMOUNT-4, a phase 3 study evaluating the safety and efficacy of Zepbound compared to placebo, had two periods.

Lead-in period: 36-week open-label period during which participants took Zepbound at the maximum tolerated dose.

Double-blind treatment period: 52-week treatment period during which participants were randomized to either continue on Zepbound or switch to placebo.

SURMOUNT-4 utilized a maximum tolerated dose of 10 mg or 15 mg once-weekly. The starting dose of 2.5 mg Zepbound was increased by 2.5 mg every four weeks until maximum tolerated dose was achieved. Participants who tolerated 15 mg continued on 15 mg as their maximum tolerated dose. Participants who tolerated 10 mg but did not tolerate 15 mg continued on 10 mg as their maximum tolerated dose.

"Patients, providers and the public do not always understand obesity is a chronic disease that often requires ongoing treatment, which can mean that treatment is stopped once weight goals are met," said Jeff Emmick, MD, Ph.D., senior vice president, product development, Lilly. "However, studies like SURMOUNT-4 show that continued therapy can help people living with obesity maintain their weight loss."... Lilly's Press Release - Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity - The SURMOUNT-4 Randomized Clinical Trial in The Journal of the American Medical Association (JAMA) - A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight for the Maintenance of Weight Loss (SURMOUNT-4) -