Surrozen Presents Preliminary Results from Phase 1a Study of SZN-043 in Healthy Volunteers and Patients with a History of Liver Cirrhosis at the 2024 European Association for the Study of the Liver (EASL) in Milan

Rhea-AI Summary

Surrozen presented preliminary Phase 1a study results of their novel drug SZN-043 at the 2024 European Association for the Study of the Liver (EASL) conference in Milan. This study involved 40 healthy volunteers and 8 liver cirrhosis patients, focusing on dose safety and tolerance. SZN-043 showed potential in increasing Wnt signaling and hepatocyte proliferation, with pharmacodynamic biomarkers confirming target engagement. Mild, transient serum transaminase elevations were noted but resolved without intervention. Current enrollment is ongoing for a Phase 1b study targeting severe alcohol-associated hepatitis, aiming to optimize Wnt pathway modulation for liver regeneration.

Positive

• Phase 1a trial showed SZN-043 was safe and well-tolerated in both healthy volunteers and liver cirrhosis patients.
• SZN-043 demonstrated Wnt-mediated pharmacodynamic activity in the liver.
• Preliminary results showed target engagement and confirmed Wnt pathway activation.
• Enrollment for a Phase 1b study in severe alcohol-associated hepatitis is ongoing.

Negative

• Some subjects experienced mild-to-moderate, transient, dose-related serum transaminase elevations.
• The serum transaminase elevations, although resolved, indicate potential liver stress that requires further monitoring.

Medical Research Analyst

Surrozen's presentation of preliminary results from the Phase 1a trial of SZN-043 offers promising insights for investors interested in biotech innovations. The significance of the results lies in the drug's ability to modulate the Wnt signaling pathway, which is a novel approach in liver disease treatment. The study's outcomes are notable for several reasons:

1. Safety and Tolerability: The fact that the drug was well-tolerated with only mild-to-moderate, transient serum transaminase elevations that resolved on their own is crucial. These elevations, a common concern with liver-targeting drugs, did not lead to any severe liver pathology, which is reassuring.

2. Pharmacodynamic Activity: Evidence of Wnt-mediated activity and target engagement is compelling. The increases in alkaline phosphatase (ALP) levels and methacetin clearance suggest that the drug is effectively engaging its target and activating the Wnt pathway. This is essential because it indicates that the drug is working as intended at a molecular level.

3. Liver Function Improvement: The observed increases in the portal hepatic filtration rate (HFR) via the HepQuant test are particularly significant. This suggests an improvement in liver function, which is the primary goal of any therapeutic targeting liver diseases.

Short-term Implications: In the short term, these results are likely to boost investor confidence and may result in a positive movement in Surrozen's stock price due to the anticipation of further successful trial phases. However, investors should remain cautious as these are preliminary results.

Long-term Implications: Long-term, if subsequent trial phases corroborate these findings, SZN-043 could become a groundbreaking therapeutic for liver diseases, potentially leading to substantial revenue growth for Surrozen. However, the path to market approval is still long and there are many hurdles to clear, including efficacy in larger population sets and regulatory approval.

As an investor, understanding the uniqueness of Wnt pathway modulation in liver therapy is essential as it differentiates Surrozen from other companies working on liver disease therapies. Continued positive results could position Surrozen as a leader in this innovative space.

Financial Analyst

Surrozen's Phase 1a trial results for SZN-043 provide several points of interest from a financial perspective.

1. Future Value Creation: If SZN-043 continues to show positive results, it could represent a significant future revenue stream for Surrozen. Investors should look at these initial findings as a preliminary indicator of potential future value.

2. Investment in R&D: Surrozen’s commitment to advancing its Wnt pathway modulation technology represents a substantial investment in research and development. The company's success hinges on the ability of this and potentially other products to move through the clinical trial stages successfully. These initial results support the notion that their R&D investment is yielding promising outcomes.

3. Market Positioning: The positive results can strengthen Surrozen’s bargaining power in potential partnerships, collaborations, or even acquisition talks. Successful phase outcomes often attract larger pharmaceutical companies looking to expand their pipeline through innovative therapies. This could create strategic opportunities for Surrozen.

Short-term Market Impact: In the short term, the stock might see a positive reaction as investors respond to the favorable news. However, one must consider the broader implications of a phase 1 trial. The drug is still far from market approval and much can change as it progresses through further trials.

Long-term Financial Outlook: Long-term investors should monitor the progression of the drug through subsequent trial phases. Success in these phases could greatly enhance Surrozen's market valuation and attract further investment. Conversely, setbacks could lead to significant volatility.

Understanding the initial success in the context of the broader clinical development timeline is crucial. As such, while these results are a positive indication, they are just the first step in a complex process that will ultimately determine the financial success of this therapeutic.

Market Research Analyst

Surrozen’s interim Phase 1a results for SZN-043 highlight essential aspects of its market potential and strategic alignment within the biotech industry.

1. Market Demand: The need for effective treatments for liver diseases, such as cirrhosis and severe alcohol-associated hepatitis, is substantial. Current treatment options are limited, making new therapies highly desirable. The positive preliminary results of SZN-043 indicate that Surrozen is addressing a significant unmet medical need, which positions the company to capture a considerable market share upon successful development and approval.

2. Competitive Edge: The innovative approach of Wnt pathway modulation gives Surrozen a competitive edge over other treatments that do not utilize this mechanism. Investors should note how this differentiation could allow Surrozen to carve out a niche within the broader market, potentially commanding a premium pricing strategy upon commercialization.

3. Regulatory Pathway: Successful early-phase results often smooth the path toward regulatory approval. Demonstrating both safety and pharmacodynamic activity is critical in gaining the confidence of regulatory bodies. These results might positively influence regulatory discussions and expedite the process, albeit still requiring rigorous scrutiny in subsequent trials.

Short-term Market Reactions: Market reactions tend to be optimistic following positive early-phase trial results. Investors might see a temporary uptick in stock price due to heightened interest and speculation on future success. However, it is important to be aware of the volatility inherent in biotech stocks at this stage of drug development.

Long-term Market Position: In the long term, if SZN-043 continues to show positive results and eventually receives approval, it could transform Surrozen’s market position. The company could transition from a developmental stage with speculative valuations to a revenue-generating entity with actual market influence and profitability.

For retail investors, it’s important to balance the immediate excitement with the understanding of the lengthy and complex drug approval process. The potential market opportunity is significant, but so are the risks involved in achieving it.

SZN-043 is a novel biotherapeutic shown to potentiate Wnt signaling and induce proliferation of hepatocytes in preclinical models

Treatment with SZN-043 in the Phase 1a trial was safe and well tolerated in healthy volunteers and patients with a history of liver cirrhosis

Phase 1a trial of SZN-043 demonstrated evidence of target engagement and Wnt-pathway mediated pharmacodynamic effects in the liver

Enrollment is ongoing in Phase 1b study in severe alcohol-associated hepatitis

SOUTH SAN FRANCISCO, Calif., June 10, 2024 (GLOBE NEWSWIRE) -- Surrozen, Inc. (“Surrozen” or the “Company”) (Nasdaq: SRZN), a company pioneering targeted therapeutics that selectively activate the Wnt Pathway for tissue repair and regeneration, presented a poster on the preliminary results of a Phase 1a study of SZN-043, a novel R-Spondin mimetic, in healthy volunteers and subjects with liver cirrhosis on June 8, 2024 at the 2024 European Association for the Study of the Liver (EASL) in Milan (LINK: HERE).  

Study Overview

• Safe and well-tolerated doses of SZN-043 were established in the randomized, placebo-controlled, first-in-human, Phase 1a trial in 40 healthy volunteers (HVs) and 8 patients with a history of liver cirrhosis.
• Single or multiple intravenous infusion doses were administered in a range from 0.5 mg/kg to 3 mg/kg.
• In some treated subjects, there were mild-to-moderate, transient, and dose-related serum transaminase elevations that resolved without intervention. These serum transaminase elevations were not associated with other changes in clinical pathology that are indicative of liver disease or bile duct damage.
  

Pharmacodynamic Biomarkers
The study provided evidence of Wnt-mediated pharmacodynamic activity in the liver after treatment with SZN-043.

1. Target engagement was confirmed via transient increases in alkaline phosphatase (ALP). Increases in ALP are indicative of SZN-043 binding to, and elimination of, its targeting receptor asialoglycoprotein (ASGPR) from the surface of the hepatocytes and this reduction in its capacity to clear ALP is consistent with observations in other ASGPR binding agents.
   
2. Wnt signal activation was demonstrated by the results of the methacetin breath test. This test showed increased methacetin clearance following SZN-043 administration which is indicative of activation of the Wnt target gene, CYP1A2, in hepatocytes.  
3. HepQuant measurements demonstrated increases in the portal hepatic filtration rate (HFR). The HepQuant test is a quantitative liver function test that measures cholate clearance to assess liver function. The increase in portal HFR is thought to be related to Wnt-mediated induction of cholate clearance by SZN-043.
   

”We were pleased to present the first clinical data from this innovative bispecific antibody-based approach to modulating the Wnt pathway. The Phase 1a study demonstrated activation of Wnt signaling, target engagement in the liver, the initial effects observed on liver function and that the drug was safe and well tolerated,” said Craig Parker, President and Chief Executive Office of Surrozen. “We are making significant progress with our platform technologies as we focus on optimizing our abilities to modulate the Wnt pathway and provide important new therapeutic options through targeted cell and tissue regeneration. Wnt modulation in hepatocytes is a promising new mechanism for supporting regeneration in injured livers.”

About SZN-043 for Severe Alcohol-Associated Hepatitis
SZN-043 is the first development candidate using Surrozen’s SWEETS™ technology. Surrozen is developing SZN-043 for severe liver diseases, initially focusing on severe alcohol-associated hepatitis. The Company has completed a Phase 1a clinical trial in patients with a history of liver cirrhosis and healthy volunteers. SZN-043 was safe and well tolerated in single or multiple IV doses and demonstrated evidence of target engagement, Wnt signal activation and effects on liver function.

The Phase 1b clinical trial in patients with severe alcohol-associated hepatitis began enrollment in the second quarter of 2024 and the Company expects that proof-of-concept data from this trial may be available in the first half of 2025. The study will enroll up to 30 patients with severe alcohol-associated hepatitis in an open-label trial. The study will evaluate safety, pharmacokinetics, immunogenicity and a number of efficacy endpoints including MELD score, Lille score and survival. The MELD and Lille scores have been shown to correlate with clinical improvement and 90-day survival.

About SZN-413 for Retinal Diseases
SZN-413 is a bi-specific antibody targeting Fzd4-mediated Wnt signaling designed using Surrozen’s SWAP™ technology. It is currently being developed for the treatment of retinal vascular-associated diseases. Data generated by Surrozen with SZN-413 in preclinical models of retinopathy demonstrated that SZN-413 could potently stimulate Wnt signaling in the eye, induce normal retinal vessel regrowth, suppress pathological vessel growth and reduce vascular leakage. This novel approach could thus potentially allow for regeneration of healthy eye tissue, not only halting retinopathy, but possibly allowing for a full reversal of the patient’s disease.

In the fourth quarter of 2022, Surrozen entered into a strategic partnership with Boehringer Ingelheim for the research and development of SZN-413 for the treatment of retinal diseases. Under the terms of the agreement, Boehringer Ingelheim received an exclusive, worldwide license to develop SZN-413 and other Fzd4-specific Wnt-modulating molecules for all purposes, including as a treatment for retinal diseases, in exchange for an upfront payment to Surrozen of $12.5 million. Surrozen will also be eligible to receive up to $587.0 million in success-based development, regulatory, and commercial milestone payments, in addition to mid-single digit to low-double digit royalties on sales. After an initial period of joint research, Boehringer Ingelheim will assume all development and commercial responsibilities.

About Wnt Signaling
Wnt signaling plays key roles in the control of development, homeostasis, and regeneration of many essential organs and tissues, including liver, intestine, lung, kidney, retina, central nervous system, cochlea, bone, and others. Modulation of Wnt signaling pathways has potential for treatment of degenerative diseases and tissue injuries. Surrozen’s platform and proprietary technologies have the potential to overcome the limitations in pursuing the Wnt pathway as a therapeutic strategy.

About Surrozen
Surrozen is a clinical stage biotechnology company discovering and developing drug candidates to selectively modulate the Wnt pathway. Surrozen is developing tissue-specific antibodies designed to engage the body’s existing biological repair mechanisms with a current focus on severe liver and eye diseases. For more information, please visit www.surrozen.com.

Forward Looking Statements
This press release contains certain forward-looking statements within the meaning of the federal securities laws. Forward-looking statements generally are accompanied by words such as “will,” “plan,” “intend,” “potential,” “expect,” “could,” or the negative of these words and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements regarding Surrozen’s discovery, research and development activities, in particular its development plans for its product candidates SZN-043 and SZN-413 (including anticipated clinical development plans and timelines, the availability of data, the potential for such product candidates to be used to treat human disease, as well as the potential benefits of such product candidates), and the Company’s partnership with Boehringer Ingelheim, including the potential for future success-based development, regulatory, and commercial milestone payments, in addition to mid-single digit to low-double digit royalties on sales. These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of the management of Surrozen and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on as a guarantee, an assurance, a prediction, or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and will differ from assumptions. Many actual events and circumstances are beyond the control of Surrozen. These forward-looking statements are subject to a number of risks and uncertainties, including the initiation, cost, timing, progress and results of research and development activities, preclinical and clinical trials with respect to SZN-043, SZN-413 and potential future drug candidates; the Company’s ability to fund its preclinical and clinical trials and development efforts, whether with existing funds or through additional fundraising; Surrozen’s ability to identify, develop and commercialize drug candidates; Surrozen’s ability to successfully complete preclinical and clinical studies for SZN-043, SZN-413, or other future product candidates; the effects that arise from volatility in global economic, political, regulatory and market conditions; and all other factors discussed in Surrozen’s Annual Report on Form 10-K for the year ended December 31, 2023 and Surrozen’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024 under the heading “Risk Factors,” and other documents Surrozen has filed, or will file, with the Securities and Exchange Commission. If any of these risks materialize or our assumptions prove incorrect, actual results could differ materially from the results implied by these forward-looking statements. There may be additional risks that Surrozen presently does not know, or that Surrozen currently believes are immaterial, that could also cause actual results to differ from those contained in the forward-looking statements. In addition, forward-looking statements reflect Surrozen’s expectations, plans, or forecasts of future events and views as of the date of this press release. Surrozen anticipates that subsequent events and developments will cause its assessments to change. However, while Surrozen may elect to update these forward-looking statements at some point in the future, Surrozen specifically disclaims any obligation to do so, except as required by law. These forward-looking statements should not be relied upon as representing Surrozen’s assessments of any date after the date of this press release. Accordingly, undue reliance should not be placed upon the forward-looking statements.

Investor and Media Contact:
Investorinfo@surrozen.com

FAQ

What are the preliminary results of Surrozen's Phase 1a study of SZN-043?

The preliminary results indicated that SZN-043 was safe and well-tolerated, showing evidence of Wnt-mediated pharmacodynamic activity and target engagement in the liver.

What did the Phase 1a trial of SZN-043 demonstrate?

The trial demonstrated Wnt-mediated pharmacodynamic effects, target engagement, and increased hepatocyte proliferation, with mild transient serum transaminase elevations in some subjects.

What is the next phase of clinical trials for SZN-043?

Enrollment is ongoing for the Phase 1b study targeting severe alcohol-associated hepatitis.

How was SZN-043 administered in the Phase 1a trial?

SZN-043 was administered via single or multiple intravenous infusions at doses ranging from 0.5 mg/kg to 3 mg/kg.

What are the pharmacodynamic biomarkers observed in the study?

The study observed transient increases in alkaline phosphatase (ALP) and increased methacetin clearance, indicating activation of the Wnt target gene CYP1A2, and improved portal hepatic filtration rate (HFR).