ASGR1

Targeted protein degradation (TPD*) technologies have demonstrated the potential to produce novel treatment approaches Surrozen’s current SWEETS bispecific antibodies are unique TPD technologies Results demonstrated that the two new ASGR-targeted SWEETS bispecific antibodies enhanced Wnt-signal activation through the unique TPD platform SOUTH SAN FRANCISCO, Calif., June 12, 2024 (GLOBE NEWSWIRE) -- Surrozen, Inc. (Nasdaq: SRZN), a company pioneering targeted therapeutics that selectively modulate the Wnt pathway for tissue repair and regeneration, announced today publication of data in eLife highlighting the potential to enhance Wnt-signal activation in new targeted SWEETS (Surrozen Wnt signal Enhancer Engineered for Tissue Specificity) bispecific antibodies which utilize a unique protein degradation platform that provides alternatives for future clinical applications (Click: HERE). This publication presented research that was focused on extending previous work by Surrozen scientists on fusing an RSPO2** mutant protein to an antibody that binds ASGR1*** which led to hepatocyte (liver cell)-specific enhanced signaling, proliferation, and restored liver function in mouse models. In this publication, the authors described the development of two new ASGR bispecific antibodies which revealed distinct epitopes on both ASGR1 and ASGR2 that resulted in a robust and cell-specific Wnt-signal activation. These ASGR-targeted SWEETS molecules represent a unique targeted protein degradation (TPD) platform, that functions via multiple mechanisms, and expands the potential opportunities to treat liver diseases through cell or tissue-specific regenerative therapeutics with enhanced Wnt signal activation. “This work published in eLIfe provides an important new approach to boost Wnt-signaling through protein degradation technologies and is an important demonstration of our continuing efforts as a company to enhance options available in areas of unmet therapeutic need including severe liver disease,” said Yang Li, Ph.D., Executive Vice President, Research at Surrozen. Surrozen also announced the publication of a review article in iScience (Click: HERE). This review article provided a comprehensive summary of work done by both Surrozen scientists and other researchers in the field on the invention of various Wnt activating platforms. This review highlights the rationales and design rules described so far and the insights learned from the studies of these novel molecules on various tissues. This review highlights the exciting progress made in this emerging field and the potential of Wnt agonists in the treatment of numerous tissue degenerative diseases. *TPD – Total protein degradation technologies focus on the complex networks of biochemical processes in protein homeostasis and includes removal of damaged proteins and targeted degradation of intracellular, extracellular, and cell-surface proteins with unwanted functions **RSPO2 = R-spondin 2***ASGR = asialoglycoprotein receptor About SZN-043 for Severe Alcohol-Associated HepatitisSZN-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. About Wnt SignalingWnt 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 SurrozenSurrozen 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 candidate SZN-043 (including anticipated clinical development plans and timelines, and the availability of data, the potential for such product candidate to be used to treat human disease, as well as the potential benefits of such product candidate), 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

-Phase 1a trial demonstrated acceptable safety and tolerability with no reported serious adverse events-Phase 1a data demonstrated target engagement, a pharmacodynamic effect and effects on liver function-Initiating Phase 1b proof-of-concept trial in severe alcohol-associated hepatitis- Expect to Present Safety, PD and PK Data for SZN-043 at Upcoming Medical Meeting in 2024 SOUTH SAN FRANCISCO, Calif., April 01, 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, today provided an update on the Phase 1a clinical trial of SZN-043 in healthy volunteers and patients with cirrhosis. The Phase 1a study was completed in February 2024. SZN-043 demonstrated acceptable safety and tolerability in all subjects, with evidence of target engagement, Wnt signal activation and effects on liver function. The observed safety and pharmacodynamic activity were the basis for the Company’s previous announcement that it planned to initiate enrollment in the Phase 1b study in alcohol-associated hepatitis. The randomized, placebo-controlled Phase 1a trial enrolled a total of 48 subjects, including 40 healthy volunteers and 8 patients with cirrhosis and a history of liver disease. Single or multiple IV doses were administered in doses ranging from 0.5mg/kg to 3 mg/kg. There were no serious adverse events nor infusion reactions observed. In the planned Phase 1b trial dose range (0.5mg/kg to 1.5 mg/kg), adverse events assessed to be drug related were mild to moderate and all resolved during the study. In healthy volunteers a few asymptomatic and transient transaminase elevations (ranging from mild to moderate) were observed which resolved without intervention, and with no clinical sequelae. There were no drug related adverse events reported in patients with cirrhosis at any dose. The pharmacokinetics of SZN-043 were consistent with our expectations and supportive of the planned doses, schedule and route of administration for alcohol-associated hepatitis. In cirrhotic patients with a history of liver disease, the Phase 1a study also demonstrated dose dependent pharmacodynamic (PD) activity through activation of Wnt signaling as assessed by the methacetin breath test. This test measures activation of the Wnt pathway via the metabolism of a Wnt target gene (CYP1A2) substrate. Target engagement was confirmed via transient increases in alkaline phosphatase (ALP). Increases in ALP are indicative of SZN-043 binding to its targeting receptor ASGR1 and reduction in its capacity to clear ALP, consistent with observations in other ASGR1 binding agents. Cirrhotic patients also showed evidence of liver function effects after treatment with SZN-043 as measured by HepQuant which is a test that measures cholate clearance, a liver specific function that quantifies liver function. ”We are excited to have observed activation of Wnt signaling, target engagement and improvement in markers of liver function during the Phase 1a studies and are pleased to advance SZN-043 into the Phase 1b clinical trial in severe alcohol-associated hepatitis. We look forward to presenting the encouraging Phase 1a data at an upcoming medical conference - the first clinical data for this innovative antibody-based approach to modulating the Wnt pathway,” said Craig Parker, President and Chief Executive Office of Surrozen. “Progress with our platform technologies supports our belief that modulation of the Wnt pathway has the potential to provide important new therapeutic options through targeted tissue regeneration.“ The Company is in the process of initiating the multi-center Phase 1b clinical trial in multiple countries and expects that proof-of-concept data from this trial may be available in the first half of 2025. The study will enroll patients with severe alcohol-associated hepatitis in an open-label trial. The Company plans to 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-043 for Severe Alcohol-Associated HepatitisSZN-043 is the first development candidate using Surrozen’s SWEETS™ technology. Surrozen is developing SZN-043 for severe liver diseases, initially focusing on alcohol-associated hepatitis. The Company has completed a Phase 1a clinical trial in patients with chronic liver disease and healthy volunteers. SZN-043 demonstrated acceptable safety and tolerability in all subjects, with evidence of target engagement, Wnt signal activation and effects on liver function. The Company is initiating the Phase 1b clinical trial in patients with severe alcohol-associated hepatitis and expects that proof-of-concept data from this trial may be available in the first half of 2025. About SZN-413 for Retinal DiseasesSZN-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 SignalingWnt 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 SurrozenSurrozen 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, and 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 or 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, 2022 and Surrozen’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 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

Researchers have translated a cutting-edge tactic for treating genetic disorders into a fresh approach for potentially stymying cancer. Cell division is the generative spark of nearly every lifeform on Earth. But if healthy growth goes unchecked, cell division can turn lethal, overwhelming the organism. Such is the case with so-called oncogenes. When altered by a mutation, these growth-moderating genes go haywire, producing a geyser of cancer cells as a result. Oncogenes are also insidiously adept at generating tumors that over time become genetically "independent" from their origin, so it has been exceedingly difficult for scientists to shut down their replication at the source. Now Rockefeller University researchers have discovered a new way to target the oncogene behind a rare and often deadly liver disease using small interfering RNAs (siRNAs), an innate mechanism for silencing gene expression. As described in Molecular Therapy, the researchers slipped siRNAs inside fibrolamellar hepatocellular carcinoma (FLC) cells through a surface receptor, where they blocked the oncogene from producing illness-inducing proteins that lead to tumor formation. It's the first time that siRNAs have been used to hobble the progression of FLC, says first author Christoph Neumayer, a Ph.D. student in Rockefeller's Laboratory of Cellular Biophysics, headed by Sanford M. Simon. But the findings have wider applications as well. "That's the really exciting part," says Neumayer. "This is proof of concept that siRNAs can be used for FLC, as well as adult liver cancers, which are much more common, and other tumor types elsewhere in the body." The fusion oncogene FLC is caused by the fusion of two genes located on chromosome 19: DNAJB1, which produces heat-shock proteins that encourage cell homeostasis, and PRKACA, which produces an enzyme called kinase A that's key to cellular metabolic function. The resulting fusion, known as DNAJB1::PRKACA, brings together the proteins and a catalytic subunit of the kinase. This dysfunctional union promotes FLC formation, but how, exactly, is still unknown. Researchers in Simon's lab discovered that this fusion caused FLC in 2014, several years after Simon's own teenage daughter, Elana, was diagnosed with liver disease. After having the resulting tumor removed -- the only treatment option available to people with FLC -- Elana went on to collaborate with her father to unearth its cause, publishing the results in Science. Since then, Simon and his group have continued to reveal the mechanisms behind the disease as well as develop therapeutics. The siRNA research is part of a three-part strategy which also includes repurposing drugs for treating FLC and using molecules known as PROTACs to selectively degrade the DNAJB1::PRKACA protein that drives FLC. The drug repurposing is in advanced preparation for a clinical trial, and some of the PROTAC work is part of an international collaboration that was just awarded a $25 million Cancer Grand Challenges grant to develop treatments for high-risk, oncogene-driven cancers in children. Recently, Simon's lab discovered that they could completely stop FLC tumor growth in mice using shRNAs, short sequences of RNA that can be engineered to disrupt mRNA. The approach also caused many tumors to shrink or disappear. Having shown that quelling the fused oncogene killed tumor cells, they decided to experiment with derailing kinase A activity, which research indicated was driving tumor growth. Unlocking the cell door The problem was, fused kinase A and its "wild type" form are nearly identical, so "any drug you developed that blocks fused kinase A activity would affect all kinase A, including in normal cells," Neumayer says. "In other words, you would incur a host of problematic side effects." They had to find a way to disable toxic kinase while containing the impact so that kinase in other cells weren't affected. To do that, they specifically designed siRNAs to aim at the fusion. But because siRNAs cannot cross cell membranes, the researchers needed to figure out a way to get the siRNA inside. Luckily, a door into the cell had already been identified: a receptor called ASGR1 that's only expressed in liver cells. Its key had been too: a binding molecule known as GalNAc. Together, the duo function as a waste disposal team. GalNAc conjugate therapies, which attach siRNA molecules to the ligand to deliver therapies inside cells, are already on the market for conditions such as hereditary transthyretin-mediated amyloidosis and atherosclerotic cardiovascular disease. The team wondered if they could use the same approach to thwart the kinase driving FLC tumors. Stabilization and shrinkage To test their theory, the researchers attached a custom siRNA to the receptor's ligand and studied the method in a variety of tumor models in mice and in human cell cultures. The conjugate therapy was not only successfully delivered into the cells in all contexts, but it also caused a reduction of mRNA in the oncogene, preventing the production of the protein and resulting in the tumors stagnating or shrinking, unable to grow. They also did not detect any liver toxicity in the mice, indicating the animals tolerated the siRNAs well. "What we saw was tumor inhibition, when we had hoped to outright kill the tumor," Neumayer notes. "Our future direction will be to try to figure out how to improve that." They also tested the specificity of the siRNA by injecting it into tumor cells of another type of liver cancer. It had no toxic impact on them -- exactly as the researchers hoped. "We wanted to show that our siRNA is so targeted to the FLC fusion oncogene that it has no side effects on other cells -- even on other cancer cells," he notes. Neumayer says the findings suggest that siRNAs may be effective beyond FLC, capable of treating tumors throughout the body with a high degree of specificity: "I think siRNA medicines as a class will have a big impact over time as a new kind of genetic therapy."