FZD5

Researchers have found a way to better control the preclinical generation of key neurons depleted in Parkinson's disease, pointing toward a new approach for a disease with no cure and few effective treatments. Researchers at the University of Toronto have found a way to better control the preclinical generation of key neurons depleted in Parkinson's disease, pointing toward a new approach for a disease with no cure and few effective treatments. The researchers used an antibody to selectively activate a receptor in a molecular signaling pathway to develop dopaminergic neurons. These neurons produce dopamine, a neurotransmitter critical to brain health. Researchers around the world have been working to coax stem cells to differentiate into dopaminergic neurons, to replace those lost in patients living with Parkinson's disease. But efforts have been hindered in part by an inability to target specific receptors and areas of the brain. "We used synthetic antibodies that we had previously developed to target the Wnt signaling pathway," said Stephane Angers, principal investigator on the study and director of the Donnelly Centre for Cellular and Molecular Biology. "We can selectively activate this pathway to direct stem cells in the midbrain to develop into neurons by targeting specific receptors in the pathway," said Angers, who is also a professor in the Leslie Dan Faculty of Pharmacy and the Temerty Faculty of Medicine, and holds the Charles H. Best Chair of Medical Research at U of T. "This activation method has not been explored before." The study was recently published in the journal Development. Parkinson's disease is the second-most common neurological disorder after Alzheimer's, affecting over 100,000 Canadians. It particularly impacts older men, progressively impairing movement and causing pain as well as sleep and mental health issues. Most previous research efforts to activate the Wnt signaling pathway have relied on a GSK3 enzyme inhibitor. This method involves multiple signaling pathways for stem cell proliferation and differentiation, which can lead to unintended effects on the newly produced neurons and activation of off-target cells. "We developed an efficient method for stimulating stem cell differentiation to produce neural cells in the midbrain," said Andy Yang, first author on the study and a PhD student at the Donnelly Centre. "Moreover, cells activated via the FZD5 receptor closely resemble dopaminergic neurons of natural origin." Another promising finding of the study was that implanting the artificially-produced neurons in a rodent model with Parkinson's disease led to improvement of the rodent's locomotive impairment. "Our next step would be to continue using rodent or other suitable models to compare the outcomes of activating the FZD5 receptor and inhibiting GSK3," said Yang. "These experiments will confirm which method is more effective in improving symptoms of Parkinson's disease ahead of clinical trials." This research was supported by the University of Toronto Medicine by Design program, which receives funding from the Canada First Research Excellence Fund, and the Canadian Institutes of Health Research.

Surrozen announced it will stop developing SZN-1326 for inflammatory bowel disease (IBD) after running into challenges finding a safe and effective dose in a Phase I trial. The news shaved off about 4% of its stock price on Thursday.The bi-specific antibody modulates Wnt signaling in target tissue by binding to particular Frizzled and LRP receptors that are highly expressed in intestinal crypts. Surrozen has said that SZN-1326 demonstrated repair of damaged intestinal epithelium and anti-inflammatory effects in preclinical models.Elevated transaminase levelsSurrozen's decision to drop the IBD programme follows the completion of a Phase I single ascending dose trial involving 37 healthy volunteers. The company said it struggled to identify an ideal dose of the drug after several participants at higher dose levels experienced asymptomatic liver enzyme increases, including four who had Grade 3 ALT and AST elevations.There were no other clinically significant lab abnormalities, and the transaminase elevations resolved spontaneously, but Surrozen had already reported that three of the four subjects had Grade 3 ALT and AST elevations back in 2022."While no safety signal was observed at lower doses, lower-dose levels would not be expected to activate Wnt signaling and produce a pharmacologic effect in the intestine," the company noted in its statement Thursday. It also pointed to broader strategic considerations, such as significant clinical development expenses and market competition in IBD.Prioritising liver disease candidateThe company said it will instead now concentrate on another investigational treatment, SZN-043 for severe liver diseases, starting with alcohol-associated hepatitis. The compound, a hepatocyte targeted R-spondin-mimetic, is designed to stimulate the regeneration of liver cells in patients with liver disease.Results from a Phase Ia trial in patients with chronic liver disease and in healthy volunteers are due this quarter. The company expects to begin enrolling patients with alcohol-associated hepatitis in a Phase Ib study this year, and says proof-of-concept data could be available in the second half.  Surrozen is also co-developing SZN-413 with Boehringer Ingelheim as a potential treatment for retinal vascular-associated diseases. The companies joined forces on the drug in 2022 under a deal worth potentially over $586.5 million.

Phase 1 clinical trials of SZN-1326 and SZN-043 initiated and ongoingPreclinical proof-of-concept data for multiple programs presented and published in Q2 continue to validate Wnt modulation for tissue repair SOUTH SAN FRANCISCO, Calif., Aug. 11, 2022 (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 reported financial results for the second quarter of 2022 and provided a corporate update. “With the initiation of clinical trials for our lead therapeutic candidates, SZN-1326 and SZN-043, Surrozen became a clinical stage company in the second quarter of 2022,” said Craig Parker, President and Chief Executive Officer of Surrozen. “During the quarter we also presented data on these programs at Digestive Disease Week, had an article on SZN-1326 published in Cellular and Molecular Gastroenterology and presented data supporting the potential of SZN-413 for the treatment of diabetic retinopathy at the Association for Research in Vision and Ophthalmology annual meeting. We look forward to continuing to advance our lead programs through the clinic, and our research programs toward the clinic.” Second Quarter 2022 & Recent Highlights Lead Product CandidatesSZN-1326 for Moderate to Severe Ulcerative Colitis SZN-1326, a Fzd5 targeted bi-specific antibody, is the first development candidate designed using Surrozen’s SWAP™ technology and targets the Wnt-signaling pathway in the intestinal epithelium. Surrozen is initially developing SZN-1326 for moderate to severe ulcerative colitis and began dosing healthy volunteers in its three-part Phase 1 clinical trial in May 2022. In preclinical animal models of acute and chronic colitis, SZN-1326 has been shown to activate Wnt signaling in the diseased intestine, stimulate intestinal epithelial regeneration, reduce inflammation and reduce disease activity with no treatment related adverse effects observed in 13-week toxicology evaluations in rats and non-human primates (NHPs). An article was recently published on SZN-1326 in Cellular and Molecular Gastroenterology. SZN-043 for Severe Alcoholic Hepatis SZN-043, a hepatocyte-specific R-spondin mimetic bispecific fusion protein targeting ASGR1, is the first development candidate using Surrozen’s SWEETS™ technology. Surrozen is developing SZN-043 for severe liver diseases, initially focusing on severe alcoholic hepatitis, and began dosing healthy volunteers in its Phase 1 clinical study in June 2022. In multiple preclinical animal models of liver injury and fibrosis, SZN-043 has been shown to selectively activate Wnt signaling in the liver, stimulate transient hepatocyte proliferation, improve liver function and reduce fibrosis with no treatment-related adverse effects observed in 4-week GLP toxicology evaluations in mice and NHPs. The Phase 1 clinical studies were posted to the Australian New Zealand Clinical Trial Registry in March 2022. Click HERE for the SZN-1326 posting and click HERE for the SZN-043 posting. Preclinical data on both programs were recently presented at Digestive Disease Week. SZN-413 for Vascular-associated Retinopathies, Including Diabetic Retinopathy and Diabetic Macular EdemaSZN-413, a Fzd4 bi-specific antibody designed using Surrozen’s SWAP™ technology, has the potential to treat retinal vascular associated diseases including diabetic retinopathy and diabetic macular edema. Surrozen recently presented data supporting the potential of SZN-413 for the treatment of retinal vascular diseases at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting. Fzd4-mediated Wnt signaling is known to play a critical role in retinal vascular integrity and function. Data with Fzd4-specific Surrozen Wnt modulating tool molecules have shown that selectively activating Wnt signaling can rescue a disease phenotype in a norrin knockout model. Recent data generated with SZN-413 in preclinical models of retinopathy demonstrated that SZN-413 stimulated Wnt signaling and was able to induce normal retinal vessel regrowth while suppressing pathological vessel growth. Research Pipeline HighlightsLacrimal GlandTear-producing glands rely on Wnt signaling for maintenance of function. Restoration of gland function through activation of Wnt signaling is a potential therapeutic approach to treat dry eye including severe dry eye associated with Sjogren’s Disease. Preclinical data demonstrated that Surrozen Wnt modulating molecules: Stimulated Wnt signaling in the lacrimal glandIncreased tear production within 2 days in a mouse IL-1a lacrimal gland injury model LungRecent discoveries of Wnt responsive progenitor cells in the lung suggest a potential role for Wnt in diseases such as Idiopathic Pulmonary Fibrosis and COPD. Preclinical data demonstrated that Surrozen Wnt modulating molecules: Stimulated Wnt signaling in the lungExpanded Alveolar AT2 cell organoidsReduced injury and improved fibrosis in an acute bleomycin mouse model About Wnt SignalingWnt signaling plays key roles in the control of development, homeostasis and regeneration of many essential organs and tissues, including liver, intestine, retina, lacrimal gland, lung, cornea, pancreas, skin 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 potential application across multiple disease areas, including inflammatory bowel disease, hepatitis, eye diseases, hearing loss, lung and airway diseases, and certain neurological disorders. For more information, please visit surrozen.com. Financial Results for the Second Quarter Ended June 30, 2022 Cash Position: Cash, cash equivalents and marketable securities for the second quarter ended June 30, 2022 were $92.7 million, compared to $104.3 million as of March 31, 2022. Research and Development Expenses: Research and development expenses for the second quarter ended June 30, 2022 were $9.6 million, as compared to $10.3 million for the same period in 2021. The decrease was primarily due to the completion of manufacturing drug substance for SZN-1326 and SZN-043 in 2021. Research and development expenses include non-cash stock-based compensation expenses of $0.4 million for the second quarter ended June 30, 2022, as compared to $0.2 million for the same period in 2021. General and Administrative Expenses: General and administrative expenses for the second quarter ended June 30, 2022 were $4.5 million, as compared to $2.4 million for the same period in 2021. The increase was primarily related to employee-related expenses, including stock-based compensation expenses, insurance costs and professional service fees, supporting the growth in our operations and costs associated with being a public company. General and administrative expenses include non-cash stock-based compensation expenses of $0.6 million for the second quarter ended June 30, 2022, as compared to $0.4 million for the same period in 2021. Interest Income: Interest income for the second quarter ended June 30, 2022 was $60,000, as compared to $7,000 for the same period in 2021. The increase was primarily related to the increase in investments in money market funds and marketable securities. Other Income, Net: Other income, net for the second quarter ended June 30, 2022 was $87,000, as compared to zero for the same period in 2021. The increase was primarily related to the gain on the change in fair value of warrant liabilities, offset by expenses related to the commitment shares issued under an equity purchase agreement. Net Loss: Net loss for the second quarter ended June 30, 2022 was $13.9 million, as compared to $12.7 million for the same period in 2021. Forward Looking StatementsThis 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 “look forward,” “will,” “plan,” “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-1326, SZN-043, and SZN-413, including anticipated clinical development timelines, and the potential for such product candidates to be used to treat human disease. 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-1326, SZN-043, SZN-413, and potential future drug candidates; Surrozen’s ability to identify, develop and commercialize drug candidates; Surrozen’s ability to successfully complete preclinical and clinical studies for SZN-1326, SZN-043, SZN-413, or other future product candidates; the effects that arise from volatility in global economic, political, regulatory and market conditions, which may be adversely affected by the conflict between Russia and Ukraine and the ongoing coronavirus (COVID-19) pandemic; and all other factors discussed in our Annual Report on Form 10-K for the year ended December 31, 2021 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 subsequent to the date of this press release. Accordingly, undue reliance should not be placed upon the forward-looking statements. Media Contact:CanaleCommIan Stone, Managing DirectorTel.: (619) 518-3518Email: ian.stone@evokegroup.com Ingrid Mezo, Account DirectorTel.: (301) 473-2881Email: ingrid.mezo@evokegroup.com Investor Contact:Email: Investorinfo@surrozen.com SURROZEN, INC.Condensed Consolidated Statements of Operations (In thousands, except per share amounts)(Unaudited) Three Months Ended June 30, Six Months Ended June 30, 2022 2021 2022 2021 Operating expenses: Research and development$9,581 $10,265 $18,952 $18,866 General and administrative 4,491 2,395 9,613 6,825 Total operating expenses 14,072 12,660 28,565 25,691 Loss from operations (14,072) (12,660) (28,565) (25,691)Interest income 60 7 109 16 Other income, net 87 — 6,584 — Net loss$(13,925) $(12,653) $(21,872) $(25,675) Net loss per share attributable to common stockholders, basic and diluted$(0.40) $(0.69) $(0.63) $(1.41) Weighted-average shares used in computing net loss per share attributable to common stockholders, basic and diluted 34,945 18,217 34,904 18,186 SURROZEN, INC.Condensed Consolidated Balance Sheets(In thousands) June 30,2022 December 31,2021(1) (Unaudited) Assets Current assets: Cash and cash equivalents$16,866 $33,091 Short-term marketable securities 75,823 68,760 Prepaid expenses and other current assets 2,130 3,338 Total current assets 94,819 105,189 Property and equipment, net 4,200 4,794 Operating lease right-of-use assets 3,837 4,582 Long-term marketable securities — 21,655 Restricted cash 405 405 Other assets 866 549 Total assets$104,127 $137,174 Liabilities and stockholders’ equity Current liabilities: Accounts payable$418 $2,718 Accrued and other liabilities 6,012 8,662 Lease liabilities, current portion 2,094 2,193 Total current liabilities 8,524 13,573 Lease liabilities, noncurrent portion 4,525 5,600 Warrant liabilities 1,382 8,301 Total liabilities 14,431 27,474 Stockholders’ equity: Preferred stock — — Common stock 4 4 Additional paid-in capital 254,689 252,464 Accumulated other comprehensive loss (476) (119)Accumulated deficit (164,521) (142,649)Total stockholders’ equity 89,696 109,700 Total liabilities and stockholders’ equity$104,127 $137,174 (1) Derived from the audited financial statements, included in the Company's Annual Report on Form 10-K for the year ended December 31, 2021.