Arrowhead Pharmaceuticals to Advance Two New RNAi-Based Obesity Candidates, ARO-INHBE and ARO-ALK7, Into Clinical Studies

Rhea-AI Summary

Arrowhead Pharmaceuticals (NASDAQ: ARWR) has announced plans to advance two new RNAi-based obesity candidates, ARO-INHBE and ARO-ALK7, into clinical studies. These candidates have shown potential in preclinical studies to reduce body weight and fat mass while preserving lean muscle mass. The company aims to submit clinical trial applications by the end of 2024 and initiate studies in early 2025.

ARO-INHBE targets the hepatic expression of the INHBE gene and Activin E production, while ARO-ALK7 targets adipose tissue expression of the ALK7 gene. Both targets are genetically validated and associated with lower risk of obesity and metabolic diseases. The company believes these novel mechanisms may represent the future of obesity treatment and management.

Positive

• Preclinical data shows potential for body weight and fat mass reduction
• Novel mechanism may lead to improved lean muscle mass preservation
• Plans to submit clinical trial applications by end of 2024
• Goal to initiate clinical studies in early 2025
• Targets (INHBE and ALK7) are genetically validated for obesity and metabolic diseases

Negative

• Candidates are still in preclinical stage, with no human trial data available
• Clinical trials have not yet begun, introducing uncertainty about efficacy and safety in humans

Insights

Medical Research Analyst

This news from Arrowhead Pharmaceuticals is highly significant for the obesity treatment landscape. The company's advancement of two novel RNAi-based candidates, ARO-INHBE and ARO-ALK7, into clinical studies represents a potential breakthrough in obesity therapeutics. The preclinical data showing reduced body weight and fat mass while preserving lean muscle mass is particularly noteworthy, as it addresses a key limitation of current obesity treatments.

The genetic validation of INHBE and ALK7 as targets associated with lower obesity risk adds credibility to this approach. If successful in clinical trials, these candidates could offer a more targeted and potentially safer alternative to existing therapies. The planned initiation of clinical studies in early 2025 puts Arrowhead on a fast track for potential market entry, which could significantly impact the competitive landscape in obesity treatment.

Financial Analyst

Arrowhead's announcement could have substantial financial implications. The global obesity treatment market is projected to reach $54 billion by 2030 and novel therapies with improved efficacy could capture a significant share. If ARO-INHBE and ARO-ALK7 demonstrate superior outcomes in clinical trials, particularly in preserving lean muscle mass, they could become preferred options for both patients and healthcare providers.

Investors should note the potential for increased valuation as these candidates progress through clinical trials. However, it's important to consider the high costs and risks associated with drug development in this competitive field. The company's ability to secure partnerships or additional funding may be critical for supporting the extensive clinical development required. The market's reaction to this news will likely be positive, but tempered by the early stage of development.

Market Research Analyst

Arrowhead's approach aligns with the growing trend towards precision medicine in obesity treatment. The focus on genetically validated targets and the potential for improved body composition outcomes could differentiate these candidates in a crowded market. The preservation of lean muscle mass is a key unmet need in current obesity treatments and if achieved, could lead to higher patient satisfaction and adherence rates.

The planned combination studies with tirzepatide are strategically sound, as they could position ARO-INHBE and ARO-ALK7 as complementary therapies to existing treatments. This approach could accelerate market adoption if successful. However, the company will face intense competition from established players and other emerging therapies. The success of these candidates will largely depend on their safety profile and long-term efficacy in clinical trials, which will be closely watched by the market.

- Company hosting an obesity/metabolic R&D webinar today, August 14, 2024, at 2:00 pm ET as Part IV of the 2024 Summer Series of R&D Webinars

PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today presented preclinical data and detailed its plans to advance two next generation RNAi-based candidates, ARO-INHBE and ARO-ALK7, into upcoming clinical studies for the treatment of obesity and metabolic diseases. In preclinical studies to date, these candidates demonstrated the potential to reduce body weight and fat mass with a novel mechanism of action that may lead to improved preservation of lean muscle mass compared to currently approved obesity therapies. Arrowhead plans to submit clinical trial applications with regulatory authorities for both programs by the end of 2024 with the goal of initiating clinical studies in volunteers with obesity in early 2025.

“Arrowhead believes that targeting the hepatic expression of the INHBE gene and the production of the Activin E ligand, and the adipose tissue expression of the ALK7 gene and the receptor it encodes, represent promising novel mechanisms to treat obesity and associated metabolic diseases. When studied as mono therapy and in combination with tirzepatide in diet induced obesity mouse models, ARO-INHBE and ARO-ALK7 both resulted in suppression of body weight and fat mass and, importantly, preservation of lean mass leading to improved body composition,” said James Hamilton, M.D., Chief of Discovery and Translational Medicine at Arrowhead. “Following the approval and positive clinical impact of new agents for obesity over the last few years, new therapeutic strategies with novel mechanisms of action are emerging that may represent the future in successful treatment and management of patients with obesity and associated diseases. We are in the final stages of preclinical development of ARO-INHBE and ARO-ALK7 and we are eager to engage with regulators by the end of this year to begin clinical studies of these exciting new medicines.”

ARO-INHBE is designed to reduce the hepatic expression of the INHBE gene and its secreted gene product, Activin E. ARO-ALK7 is designed to reduce the adipose expression of Activin receptor-like kinase 7 (ALK7). INHBE and ALK7 are both genetically validated targets with loss of function variants being associated with lower risk of obesity and metabolic diseases, such as type 2 diabetes. Both targets are involved in the same pathway that regulates energy homeostasis in adipose tissue​, with Activin E acting as a circulating ligand and ALK7 as a receptor on adipocytes. Intervening in this pathway with ARO-INHBE and ARO-ALK7 is believed to result in increased lipolysis, and reductions in adipose hypertrophy and dysfunction, visceral adiposity, and insulin resistance.

To learn more about ARO-INHBE and ARO-ALK7, please join Part IV of Arrowhead’s 2024 Summer Series of R&D Webinars, being held today, August 14, 2024, at 2:00 PM ET. The event will feature Arrowhead management and Carel le Roux, M.D., Ph.D., from University College Dublin. The live event and an archived webcast may be accessed on the Events and Presentations page in the Investors section of the Arrowhead website.

About Arrowhead Pharmaceuticals

Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing.

For more information, please visit www.arrowheadpharma.com, or follow us on X (formerly Twitter) at @ArrowheadPharma or on LinkedIn. To be added to the Company's email list and receive news directly, please visit http://ir.arrowheadpharma.com/email-alerts.

Safe Harbor Statement under the Private Securities Litigation Reform Act:

This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Any statements contained in this release except for historical information may be deemed to be forward-looking statements. Without limiting the generality of the foregoing, words such as “may,” “will,” “expect,” “believe,” “anticipate,” “hope,” “intend,” “plan,” “project,” “could,” “estimate,” “continue,” “target,” “forecast” or “continue” or the negative of these words or other variations thereof or comparable terminology are intended to identify such forward-looking statements. In addition, any statements that refer to projections of our future financial performance, trends in our business, expectations for our product pipeline or product candidates, including anticipated regulatory submissions and clinical program results, prospects or benefits of our collaborations with other companies, or other characterizations of future events or circumstances are forward-looking statements. These forward-looking statements include, but are not limited to, statements about the initiation, timing, progress and results of our preclinical studies and clinical trials, and our research and development programs; our expectations regarding the potential benefits of the partnership, licensing and/or collaboration arrangements and other strategic arrangements and transactions we have entered into or may enter into in the future; our beliefs and expectations regarding milestone, royalty or other payments that could be due to or from third parties under existing agreements; and our estimates regarding future revenues, research and development expenses, capital requirements and payments to third parties. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of numerous factors and uncertainties, including the impact of the ongoing COVID-19 pandemic on our business, the safety and efficacy of our product candidates, decisions of regulatory authorities and the timing thereof, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, the enforcement of our intellectual property rights, and the other risks and uncertainties described in our most recent Annual Report on Form 10-K, subsequent Quarterly Reports on Form 10-Q and other documents filed with the Securities and Exchange Commission from time to time. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances.

Source: Arrowhead Pharmaceuticals, Inc.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240814618768/en/

Arrowhead Pharmaceuticals, Inc.

Vince Anzalone, CFA

626-304-3400

ir@arrowheadpharma.com

Investors:

LifeSci Advisors, LLC

Brian Ritchie

212-915-2578

britchie@lifesciadvisors.com

Media:

LifeSci Communications, LLC

Kendy Guarinoni, Ph.D.

724-910-9389

kguarinoni@lifescicomms.com

Source: Arrowhead Pharmaceuticals, Inc.

FAQ

What are Arrowhead Pharmaceuticals' new obesity candidates?

Arrowhead Pharmaceuticals' new obesity candidates are ARO-INHBE and ARO-ALK7, which are RNAi-based therapeutics designed to target the INHBE gene and ALK7 gene, respectively.

When does Arrowhead plan to start clinical trials for ARO-INHBE and ARO-ALK7?

Arrowhead plans to submit clinical trial applications by the end of 2024 and aims to initiate clinical studies in volunteers with obesity in early 2025.

What potential benefits do ARO-INHBE and ARO-ALK7 show in preclinical studies?

In preclinical studies, ARO-INHBE and ARO-ALK7 demonstrated potential to reduce body weight and fat mass while potentially preserving lean muscle mass better than currently approved obesity therapies.

How do ARO-INHBE and ARO-ALK7 differ from current obesity treatments?

ARO-INHBE and ARO-ALK7 represent novel mechanisms of action that target specific genes (INHBE and ALK7) involved in energy homeostasis in adipose tissue, potentially offering improved body composition outcomes compared to existing therapies.