Eine Serie-D-Finanzierung in Höhe von 100 Millionen US-Dollar: Avalyn Pharma knackt das Problem der Lungenfibrose-Behandlung mit Inhalationstherapie

Recently, Avalyn Pharma, a biotech company focused on the development of inhaled therapies for pulmonary fibrosis, announced the successful completion of an oversubscribed $100 million Series D financing round. This financing was co-led by Suvretta Capital Management and SR One, with participation from existing investors such as Norwest Venture Partners and Perceptive Advisors.

The funds from this round will primarily support Avalyn's key clinical progress in the field of pulmonary fibrosis treatment. This includes advancing the global Phase IIb clinical trial of its core candidate drug AP01 (inhaled pirfenidone), the late-stage development of AP02 (inhaled nintedanib), and the entry of AP03 (pirfenidone/nintedanib fixed-dose combination) into the Phase I clinical stage. Through parallel investment in these three products, Avalyn is gradually building a diversified product portfolio in the field of inhaled anti-fibrotic therapies.

Inhaled Delivery + Local Targeting: Creating a New Path to Reduce Toxicity and Maintain Efficacy

In the field of rare lung disease treatment, idiopathic pulmonary fibrosis (IPF) is like an insurmountable fortress. This interstitial lung disease, which has an insidious onset and rapid progression, has a disease course comparable to that of malignant tumors. The median survival time of patients is only 3 - 5 years [1]. More than 200 pathological types of interstitial lung disease (ILD) often progress to pulmonary fibrosis, seriously threatening the lives and health of patients. Although anti-fibrotic drugs such as pirfenidone and nintedanib have been approved, the common side effects and limited compliance associated with oral formulations have become a major obstacle in patients' treatment journey.

Avalyn Pharma entered the scene in this context, attempting to find a better solution between efficacy and long-term tolerance by establishing a treatment path of "inhaled delivery + local targeting".

Its core technical strategy is to redevelop existing drugs that have been proven effective but have significant side effects due to systemic exposure into inhaled formulations. The drugs are precisely deposited in the alveolar area with the help of a fine-particle nebulizer, bypassing gastrointestinal absorption and first-pass liver metabolism, significantly reducing systemic toxicity and increasing the local concentration in the lungs. This not only achieves the goal of "reducing toxicity and maintaining efficacy" but also provides a long-term treatment option for patients with fibrotic chronic diseases.

From Single-Drug Optimization to Combination Therapy: Building a Diverse Pipeline of Inhaled Therapies

Avalyn has currently built a candidate drug portfolio centered around AP01, AP02, and AP03 based on its inhaled anti-fibrotic platform, aiming to address two key challenges in the treatment of pulmonary fibrosis: insufficient efficacy and frequent systemic adverse reactions.

Figure 1: Overview of Avalyn's Pipeline (Source: Avalyn's official website)

■ AP01: The First Core Product, Redefining the Safety and Compliance of Pirfenidone

Pirfenidone, a clinically proven anti-fibrotic drug, can exert anti-inflammatory and anti-fibrotic effects by regulating cytokines and growth factors. However, the oral formulation has significant limitations: systemic exposure leads to frequent side effects such as gastrointestinal discomfort and skin reactions. In clinical practice, the dose often needs to be reduced to control toxicity, which inevitably weakens the efficacy, creating a "efficacy - toxicity" treatment dilemma.

Avalyn has reformulated oral pirfenidone into an inhaled dosage form, using the FDA-approved eFlow nebulizer for soft mist delivery. This technology allows the drug to be directly deposited in the alveolar area in fine particles. Compared with the oral formulation, while reducing the dose, it precisely targets the lung lesions - bypassing gastrointestinal absorption and first-pass liver metabolism and avoiding the side effects caused by systemic circulation, achieving the delivery advantage of "high concentration in the lungs and low systemic exposure".

In the completed Phase Ib clinical study, AP01 showed good safety and tolerability [2]. Currently, AP01 is recruiting patients for a global multi-center Phase IIb clinical trial, aiming to further evaluate its efficacy and safety in the target patient population and provide a basis for the subsequent pivotal Phase III study.

■ AP02: Inhaled Nintedanib, Expanding the Applicability of the Patient Population

Nintedanib, a multi-targeted tyrosine kinase inhibitor, can effectively block the progression of pulmonary fibrosis. However, systemic exposure through oral administration leads to a relatively high incidence of adverse reactions such as diarrhea, hyperbilirubinemia, and drug-induced liver injury.

AP02, an inhaled dosage form of nintedanib, has been developed by reconfiguring the drug delivery route using inhaled delivery technology. With a dedicated nebulizer, the drug acts directly on the lung lesions, significantly reducing systemic exposure.

Currently, AP02 has completed the Phase I clinical trials of single ascending dose (SAD) and multiple ascending dose (MAD). The trial demonstrated safety, tolerability, and good pharmacokinetic characteristics at all dose levels. Notably, clinical data showed that compared with a 150 mg oral dose, a single 4 mg dose of AP02 resulted in more than 20 times higher lung exposure.

Avalyn positions AP02 as an important complement to AP01, targeting patients who have insufficient efficacy or intolerance to pirfenidone, especially those with progressive pulmonary fibrosis (PPF) and systemic sclerosis-related interstitial lung disease (SSc-ILD). It is planned to advance AP02 to a Phase II clinical trial for IPF indications, and subsequently form a differentiated combination strategy with AP01 based on efficacy and tolerability data.

■ AP03: An Early-Stage Project in Multi-Targeted Combination Development

Clinical studies have shown that although the combined oral administration of pirfenidone and nintedanib may enhance the anti-fibrotic effect, the superimposed systemic toxicity (such as an increased risk of liver injury) makes combination therapy unfeasible in clinical practice. The traditional oral route cannot resolve the contradiction between "synergistic efficacy" and "toxicity accumulation", which has become an important technical barrier in anti-fibrotic treatment.

AP03 adopts a "fixed-dose inhaled combination" strategy, delivering the two drugs simultaneously through aerosol pulmonary delivery technology. This design takes advantage of the local targeting characteristics of inhaled therapy to create a synergistic effect of the drugs in the lung lesions while avoiding the toxicity accumulation associated with systemic combination therapy. Preclinical data showed that this combination exhibited better anti-fibrotic effects than single drugs in animal models, and no new side effects were observed.

Currently, Avalyn is advancing the IND support study for AP03 and plans to conduct a Phase I clinical trial. Although it is still in the preclinical stage, this project reflects Avalyn's continuous innovation path of "precise delivery + multi-targeted synergy" at the platform level and has the potential to expand to a broader spectrum of diseases.

Overall, Avalyn is leveraging its differentiated inhaled delivery platform to build a diverse product portfolio in the highly unmet field of pulmonary fibrosis. It has achieved a positive synergy among improving efficacy, optimizing safety, and expanding the scope of indications, demonstrating a strong technological moat and commercialization potential.

Supported by Four Rounds of Financing, Collaborating in Clinical and Regulatory Efforts

Since its establishment in Seattle in 2011, Avalyn has rapidly grown from a small startup focused on nebulized delivery technology to a clinical-stage biopharmaceutical company with a complete pipeline of candidate drugs and the ability to operate an ecosystem.

Since the platform construction stage, Avalyn Pharma has received high recognition from capital. It has completed a total of four rounds of financing, raising more than $300 million in total, providing strong support for advancing the development of its core pipeline, expanding clinical trials, and building the platform ecosystem.

Table 1: Overview of Avalyn's Financing (Source: Avalyn's official website)

Driven by financing, Avalyn has simultaneously built a complete ecosystem. On the one hand, Avalyn collaborates with the US ILD Collaborative Research Network and several university-affiliated hospitals to conduct clinical research, ensuring data quality and clinical efficiency.

On the other hand, its leading product, AP01, has received Fast Track designation from the FDA, accelerating the approval process. Avalyn has also initiated preparations for commercialization, such as building a production base and validating the supply chain, laying the foundation for rapid product delivery after future approval.

With the collaborative efforts of financing, clinical research, regulatory affairs, and commercial capabilities, Avalyn is steadily transitioning from a platform incubation stage to a clinical product-driven enterprise, building a competitive product matrix for inhaled lung therapies.

Although the current treatment options for pulmonary fibrosis are limited, with companies like Avalyn continuously advancing the development of locally targeted drugs, a new generation of safer, long-term, and more compliant therapies may emerge in the future.

References:

[1] Lederer DJ, Martinez FJ. Idiopathic Pulmonary Fibrosis. N Engl J Med. 2018 May 10;378(19):1811-1823. doi: 10.1056/NEJMra1705751. PMID: 29742380.

[2] West A, Chaudhuri N, Barczyk A, et al. Inhaled pirfenidone solution (AP01) for IPF: a randomised, open-label, dose–response trial. Thorax 2023;78:882-889.

This article is from the WeChat official account "Arterial Network" (ID: vcbeat). Author: Huang Yurou. Republished by 36Kr with permission.