Vedolizumab

Total Revenues in the first nine months of 2024 increased by $300 million compared to same period in 2023, to $339 million, with Q3 revenues contributing $103 millionProduct revenues in the first nine months of 2024 increased over four-fold compared to the same period last year, to $128 million, with Q3 product revenues contributing $62 millionLicense and other revenues for the first nine months of 2024 increased by $203 from the same period last year, to $211 million, with Q3 license and other revenues contributing $41 millionAdjusted EBITDA was $87 million in the first nine months of 2024, compared to negative ($225) million for the same period last year, with Q3 adjusted EBITDA contributing $23 millionMarketing applications were accepted in Europe for biosimilar candidates to Prolia®/Xgeva® (denosumab) and Simponi (golimumab) and Alvotech initiated a confirmatory clinical study for AVT16, a biosimilar candidate to Entyvio® (vedolizumab)Alvotech will conduct a business update conference call and live webcast on Thursday, November 14, 2024, at 8:00 am ET (13:00 GMT) Alvotech (NASDAQ: ALVO, or the “Company”), a global biotech company specializing in the development and manufacture of biosimilar medicines for patients worldwide, today reported unaudited financial results for the first nine months of 2024 and provided a summary of recent corporate highlights. “We are delighted by the results in the quarter and the first nine months of 2024. The third quarter marked our second consecutive quarter with positive adjusted EBITDA and operating profit. Not only did we see growth in product revenue compared to the previous quarter, but we also experienced a more than doubling of product gross margins, primarily due to improved utilization and scale at our manufacturing site,” said Robert Wessman, Chairman and CEO of Alvotech. “We are also pleased with the steady progress of our pipeline, which included multiple filing acceptances in Europe and the initiation of our confirmatory clinical study for AVT16, our proposed biosimilar to Entyvio. The continued execution of our research and development activities not only contributes to our topline through milestone revenues but also provides further opportunities for the company to grow and diversify in the future.” Product development highlights Alvotech announced that the European Medicines Agency (EMA) accepted a Marketing Authorization Application (MAA) for AVT03, a proposed biosimilar to Prolia® and Xgeva® (denosumab) and an MAA for AVT05, a proposed biosimilar to Simponi® (golimumab). For European markets, Alvotech has partnership agreements for commercialization of AVT03 with STADA and Dr. Reddy’s Laboratories and for AVT05 with Advanz Pharma. Alvotech announced the initiation of a confirmatory patient study for AVT16, a proposed biosimilar to Entyvio® (vedolizumab). Entyvio, which generated approximately $5.4 billion in global sales in the twelve months until June 30, 2024 [1], is used to treat ulcerative colitis and Crohn’s disease [2]. Alvotech and Teva Pharmaceuticals announced that the U.S. FDA has approved a new presentation of SELARSDI™ (ustekinumab-aekn), a biosimilar to Stelara® (ustekinumab), in a 130 mg/26 mL single-dose vial for intravenous infusion. This approval also expands SELARSDI's label to include treatment for adults with Crohn’s disease and ulcerative colitis, aligning it with the reference product's indications. The U.S. launch of SELARSDI is expected in February 2025. Summary of the Financial Results for First Nine Months of 2024 Cash position and sources of liquidity: As of September 30, 2024, the Company had cash and cash equivalents of $118.3 million. In addition, the Company had borrowings of $1,028.2 million, including $22.2 million of current portion of borrowings. Product Revenue: Product revenue was $128.0 million for the nine months ended September 30, 2024, compared to $29.8 million for the same nine months of 2023. Revenue for the nine months ended September 30, 2024, consisted of product revenue from sales of AVT02 in select European countries and Canada, launch of AVT02 in the U.S., and launch of AVT04 in Canada, Japan and select European markets. License and Other Revenue: License and other revenue was $210.5 million for the nine months ended September 30, 2024, compared to $8.2 million for the same nine months of 2023. The license and other revenue of $210.5 million was primarily attributable to the recognition of a $6.6 million research and development milestone due to the approval of AVT04 in Europe, $16.8 million relative to research and development milestone due to the commencement of a clinical phase for the AVT16 program, $22.3 million due to the MAA submission for AVT03 and AVT06, and $95.6 million due to the Confirmatory Efficacy and Safety (CES) trial completion of AVT03 and AVT05. This also included $41.1 million of performance milestone relative to the product launch of AVT04 in Japan and Europe, the achievement of sales target of AVT02 in Europe and Canada, and the product launch of AVT02 in the U.S., and a net milestone revenue of $26.4 million for the execution of out-license contracts during the nine months ended September 30, 2024. Cost of product revenue: Cost of product revenue was $105.0 million for the nine months ended September 30, 2024, compared to $104.4 million for the same nine months of 2023, as a result of sales in the period, including the launch of AVT02 in the U.S., AVT04 in Canada, Japan and select European countries tempered by lower production-related charges and lower costs associated with FDA inspection readiness. Research and development (R&D) expenses: R&D expenses were $131.1 million for the nine months ended September 30, 2024, compared to $152.8 million for the same nine months of 2023. The decrease was primarily driven by a one-time charge of $18.5 million relating to the termination of the co-development agreement with Biosana for AVT23 recognized during the nine months of 2023, a decrease of $4.3 million primarily related to programs which have completed clinical phase (i.e., AVT02 and AVT04 programs), a decrease of $6.0 million related to programs for which the clinical phase is substantially completed (i.e. AVT03, AVT05, and AVT06), and overall lower headcount and other R&D expenses of $11.4 million, partially offset by a $17.4 million increase in direct program expenses mainly due to AVT16 that is in clinical phase. General and administrative (G&A) expenses: G&A expenses were $46.4 million for the nine months ended September 30, 2024, compared to $58.6 million for the same nine months of 2023. The decrease in G&A expenses was primarily attributable to $6.6 million in lower third-party services, lower insurance premiums and less headcount, coupled with a $4.6 million decrease in expenses for share-based payments. Operating profit: Operating profit was $56.2 million for the nine months ended September 30, 2024, compared to ($277.7) million for the same nine months of 2023. The increase of $333.9 million was primarily attributable to the sharp increase in total revenues due to a combination of expansion of our product launches and milestones recognition for advancing our product through our pipeline and achieving contractual sales targets. This is coupled with a decrease in operating expenses driven by continuing efforts by the Company to scale and rationalize operations. Share of net loss of joint venture and loss on interest in joint venture: In June 2024, Alvotech sold its share in the joint venture for gross proceeds of $18.0 million (less $1.3 million in transaction costs). The sale resulted in a net loss of $3.0 million during the nine months ended 30 September 2024. Finance income: Finance income was $79.1 million for the nine months ended September 30, 2024, compared to $46.4 million for the same nine months of 2023. Finance income for the nine months ended September 30, 2024, was primarily attributable to the change in fair value of the Tranche A Conversion Feature of the 2022 Convertible bonds impacted by the bond holders exercising their right to conversion into ordinary shares on the last scheduled conversion date prior to maturity, which was July 1, 2024. The Finance income for the nine months ended September 30, 2023, was mainly attributable to a favorable change in fair value of the Predecessors Earn Out shares. Finance costs: Finance costs were $237.7 million for the nine months ended September 30, 2024, compared to $107.8 million for the same nine months of 2023. The Finance costs for the nine months ended September 30, 2024, were primarily comprised of a $107.3 million change in fair value of the Predecessors Earn Out shares, which was negatively impacted by the increase in the Company's share price during that period, and by interest charges on outstanding debts of $115.0 million. . Exchange rate differences: Exchange rate differences resulted in a gain of $1.7 million for the nine months ended September 30, 2024, compared to a gain of $0.9 million for the same nine months of 2023. The change was primarily driven by the movements in the exchange rate of the dollar against other currencies, predominantly Icelandic krona and euros. Loss on extinguishment of financial liabilities: On June 7, 2024, the Company entered into a $965.0 million Facility, maturing in July 2029, that was funded in July 2024. Upon the closing of the Facility, the Company was required to settle its existing debt obligations. In parallel, the Company announced that all holders of the Tranche A and some holders of the Tranche B of the 2022 Convertible Bonds exercised their right to conversion into ordinary shares at the fixed conversion price of $10.00 per share on the last scheduled conversion date prior to maturity, which is July 1, 2024. Similarly, some holders of the Aztiq Convertible Bonds decided to exercise similar conversion right into ordinary shares at the same conversion price. A loss on extinguishment of financial liabilities of $69.0 million related to the refinancing of existing debt obligations, including the conversion of the 2022 Convertible Bonds and Aztiq Convertible Bonds, was recorded during the nine months ended September 30, 2024. Income tax benefit: Income tax benefit was $8.2 million for the nine months ended September 30, 2024, compared to a benefit of $67.1 million for the same nine months of 2023. The decrease in benefit was mainly driven by a decrease of $61.1 million in deferred tax credit corresponding to lower operating losses and a $4.2 million decrease in foreign currency impact on the strengthening of the Icelandic Krona against the U.S. Dollar, increasing the U.S. Dollar value of Icelandic tax loss carry-forwards that Alvotech expects to utilize against future taxable profits. The decrease in income tax benefit is partly offset by an increase in other permanent differences of approximately $7.0 million. Loss for the Period: Reported net loss was $164.9 million, or ($0.63) per share on a basic and diluted basis, for the nine months ended September 30, 2024, compared to a reported net loss of $275.2 million, or ($1.21) per share on a basic and diluted basis, for the same nine months of 2023. As mentioned above, the net loss for the period is heavily impacted by the non-cash fair value charges associated with our derivative liabilities and the impact of the refinancing of the existing debt obligations. Business Update Conference Call Alvotech will conduct a business update conference call and live webcast on Thursday, November 14, at 8:00 am ET (13:00 pm GMT). Registration for the conference call and access to the live webcast is found on https://investors.alvotech.com/events/event-details/q3-2024-earnings, where you will also be able to find a replay of the webcast, following the call for 90 days. About AVT02 (adalimumab) AVT02 is a monoclonal antibody and has been approved as a biosimilar to Humira® (adalimumab) in over 50 countries globally, including the U.S., Europe, Canada, Australia, Egypt, Saudi Arabia and South Africa. It is currently marketed in the U.S. as SIMLANDI and under private label (adalimumab-ryvk), in Europe as HUKYNDRA, in Canada as SIMLANDI and in Australia as ADALACIP. Dossiers are also under review in multiple countries globally. About AVT03AVT03 is a human monoclonal antibody and a biosimilar candidate to Prolia® and Xgeva® (denosumab). Denosumab targets and binds with high affinity and specificity to the RANK ligand membrane protein, preventing the RANK ligand/RANK interaction from occurring, resulting in reduced osteoclast numbers and function, thereby decreasing bone resorption and cancer-induced bone destruction [3]. AVT03 is an investigational product and has not received regulatory approval in any country. Biosimiliarity has not been established by regulatory authorities and is not claimed. About AVT04 (ustekinumab) AVT04 is a monoclonal antibody and a biosimilar to Stelara® (ustekinumab). Ustekinumab binds to two cytokines, IL-12 and IL-23, that are involved in inflammatory and immune responses [4]. AVT04 has been launched in Canada as JAMTEKI, in the EEA as UZPRUVO, and in Japan as USTEKINUMAB BS (F). It has been approved in the U.S. as SELARSDI (ustekinumab-aekn). Dossiers are also under review in multiple countries globally. About AVT06/AVT29AVT06/AVT29 is a recombinant fusion protein and a biosimilar candidate to Eylea® (aflibercept) 2 mg and 8 mg dose, which binds vascular endothelial growth factors (VEGF), inhibiting the binding and activation of VEGF receptors, neovascularization, and vascular permeability [5]. AVT06/AVT29 are investigational products and have not received regulatory approval in any country. Biosimilarity has not been established by regulatory authorities and is not claimed. About AVT16 AVT16 is a human monoclonal antibody and a biosimilar candidate to Entyvio® (vedolizumab). AVT16 is an investigational product and has not received regulatory approval in any country. Biosimiliarity has not been established by regulatory authorities and is not claimed. Sources [1] IQVIA [2] Entyvio product information[3] Prolia product information[4] Uzpruvo product information[5] Eylea product information Use of trademarks Humira is a registered trademark of AbbVie Inc. Stelara is a registered trademark of Johnson & Johnson Inc. Prolia and Xgeva are registered trademarks of Amgen Inc. Elyea is a registered trademark of Regeneron Pharmaceuticals Inc. and Bayer AG. Entyvio is a registered trademark of Millenium Pharmaceuticals Inc. About Alvotech Alvotech is a biotech company, founded by Robert Wessman, focused solely on the development and manufacture of biosimilar medicines for patients worldwide. Alvotech seeks to be a global leader in the biosimilar space by delivering high quality, cost-effective products, and services, enabled by a fully integrated approach and broad in-house capabilities. Alvotech has launched two biosimilars. The current development pipeline includes nine disclosed biosimilar candidates aimed at treating autoimmune disorders, eye disorders, osteoporosis, respiratory disease, and cancer. Alvotech has formed a network of strategic commercial partnerships to provide global reach and leverage local expertise in markets that include the United States, Europe, Japan, China, and other Asian countries and large parts of South America, Africa and the Middle East. Alvotech’s commercial partners include Teva Pharmaceuticals, a US affiliate of Teva Pharmaceutical Industries Ltd. (US), STADA Arzneimittel AG (EU), Fuji Pharma Co., Ltd (Japan), Advanz Pharma (EEA, UK, Switzerland, Canada, Australia and New Zealand), Dr. Reddy’s (EEA, UK and US), Biogaran (FR), Cipla/Cipla Gulf/Cipla Med Pro (Australia, New Zealand, South Africa/Africa), JAMP Pharma Corporation (Canada), Yangtze River Pharmaceutical (Group) Co., Ltd. (China), DKSH (Taiwan, Hong Kong, Cambodia, Malaysia, Singapore, Indonesia, India, Bangladesh and Pakistan), YAS Holding LLC (Middle East and North Africa), Abdi Ibrahim (Turkey), Kamada Ltd. (Israel), Mega Labs, Stein, Libbs, Tuteur and Saval (Latin America) and Lotus Pharmaceuticals Co., Ltd. (Thailand, Vietnam, Philippines, and South Korea). Each commercial partnership covers a unique set of product(s) and territories. Except as specifically set forth therein, Alvotech disclaims responsibility for the content of periodic filings, disclosures and other reports made available by its partners. For more information, please visit www.alvotech.com. None of the information on the Alvotech website shall be deemed part of this press release. Please visit our investor portal, and our website or follow us on social media on LinkedIn, Facebook, Instagram, X and YouTube. Alvotech Forward Looking Statements Certain statements in this communication may be considered “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements generally relate to future events or the future financial operating performance of Alvotech and may include, for example, Alvotech’s expectations regarding competitive advantages, business prospects and opportunities including pipeline product development, future plans and intentions, results, level of activities, performance, goals or achievements or other future events, regulatory submissions, review and interactions, the potential approval and commercial launch of its product candidates, the timing of regulatory approval, and market launches. In some cases, you can identify forward-looking statements by terminology such as “may”, “should”, “expect”, “intend”, “will”, “estimate”, “anticipate”, “believe”, “predict”, “potential”, “aim” or “continue”, or the negatives of these terms or variations of them or similar terminology. Such forward-looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward-looking statements. These forward-looking statements are based upon estimates and assumptions that, while considered reasonable by Alvotech and its management, are inherently uncertain and are inherently subject to risks, variability, and contingencies, many of which are beyond Alvotech’s control. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: (1) the ability to raise substantial additional funding, which may not be available on acceptable terms or at all; (2) the ability to maintain stock exchange listing standards; (3) changes in applicable laws or regulations; (4) the possibility that Alvotech may be adversely affected by other economic, business, and/or competitive factors; (5) Alvotech’s estimates of expenses and profitability; (6) Alvotech’s ability to develop, manufacture and commercialize the products and product candidates in its pipeline; (7) actions of regulatory authorities, which may affect the initiation, timing and progress of clinical studies or future regulatory approvals or marketing authorizations; (8) the ability of Alvotech or its partners to respond to inspection findings and resolve deficiencies to the satisfaction of the regulators; (9) the ability of Alvotech or its partners to enroll and retain patients in clinical studies; (10) the ability of Alvotech or its partners to gain approval from regulators for planned clinical studies, study plans or sites; (11) the ability of Alvotech’s partners to conduct, supervise and monitor existing and potential future clinical studies, which may impact development timelines and plans; (12) Alvotech’s ability to obtain and maintain regulatory approval or authorizations of its products, including the timing or likelihood of expansion into additional markets or geographies; (13) the success of Alvotech’s current and future collaborations, joint ventures, partnerships or licensing arrangements; (14) Alvotech’s ability, and that of its commercial partners, to execute their commercialization strategy for approved products; (15) Alvotech’s ability to manufacture sufficient commercial supply of its approved products; (16) the outcome of ongoing and future litigation regarding Alvotech’s products and product candidates; (17) the impact of worsening macroeconomic conditions, including rising inflation and interest rates and general market conditions, conflicts in Ukraine, the Middle East and other global geopolitical tension, on the Company’s business, financial position, strategy and anticipated milestones; and (18) other risks and uncertainties set forth in the sections entitled “Risk Factors” and “Cautionary Note Regarding Forward-Looking Statements” in documents that Alvotech may from time to time file or furnish with the SEC. There may be additional risks that Alvotech does not presently know or that Alvotech currently believes are immaterial that could also cause actual results to differ from those contained in the forward-looking statements. Nothing in this communication should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements, which speak only as of the date they are made. Alvotech does not undertake any duty to update these forward-looking statements or to inform the recipient of any matters of which any of them becomes aware of which may affect any matter referred to in this communication. Alvotech disclaims any and all liability for any loss or damage (whether foreseeable or not) suffered or incurred by any person or entity as a result of anything contained or omitted from this communication and such liability is expressly disclaimed. The recipient agrees that it shall not seek to sue or otherwise hold Alvotech or any of its directors, officers, employees, affiliates, agents, advisors, or representatives liable in any respect for the provision of this communication, the information contained in this communication, or the omission of any information from this communication. ALVOTECH INVESTOR RELATIONS AND GLOBAL COMMUNICATIONS Benedikt Stefansson, VPalvotech.ir@alvotech.com Unaudited Condensed Consolidated Interim Statements of Profit or Loss and Other Comprehensive Income or LossUSD in thousands, except for per share amountsNine months ended30 September 2024Nine months ended30 September 2023Product revenue 128,018 29,800License and other revenue 210,459 8,244Other income160 56Cost of product revenue (104,979) (104,437)Research and development expenses (131,050) (152,813)General and administrative expenses (46,435) (58,558)Operating profit / (loss) 56,173 (277,708)Share of net loss of joint venture — (3,983)Loss on sale of investment in joint venture (2,970) —Finance income 79,079 46,383Finance costs (237,683) (107,826)Exchange rate differences 1,657 884Loss on extinguishment of financial liabilities (69,378) —Non-operating loss (229,295) (64,542)Loss before taxes (173,122) (342,250)Income tax benefit 8,225 67,076Loss for the period (164,897) (275,174)Other comprehensive (loss) Item that will be reclassified to profit or loss in subsequent periods: Exchange rate differences on translation of foreign operations 1,347 (2,648)Total comprehensive loss (163,550) (277,822)Loss per share Basic and diluted loss for the year per share (0.63) (1.21) Unaudited Condensed Consolidated Interim Statements of Financial PositionUSD in thousands Non-current assets30 September 202430 September 2023Property, plant and equipment 255,838 236,779Right-of-use assets 153,044 119,802Goodwill 12,201 12,058Other intangible assets 20,538 19,076Contract assets 28,828 10,856Interest in joint venture — 18,494Other long-term assets 9,524 2,244Restricted cash — 26,132Deferred tax assets 320,369 309,807Total non-current assets 800,342 755,248urrent assets Inventories 125,014 74,433Trade receivables 77,420 41,292Contract assets 68,128 35,193Other current assets 43,729 31,871Receivables from related parties 41 896Cash and cash equivalents 118,274 11,157Total current assets 432,606 194,842Total assets 1,232,948 950,090 Unaudited Condensed Consolidated Interim Statements of Financial PositionUSD in thousandsEquity30 September 202430 September 2023Share capital 2,825 2,279Share premium 2,007,784 1,229,690Other reserves 16,607 42,911Translation reserve (181) (1,528)Accumulated deficit (2,370,742) (2,205,845)Total equity (343,707) (932,493)Non-current liabilities Borrowings 1,005,940922,134Derivative financial liabilities 182,361 520,553Lease liabilities 140,762 105,632Contract liabilities 85,502 73,261Deferred tax liability 1,541 53Total non-current liabilities 1,416,106 1,621,633Current liabilities Trade and other payables 57,720 80,563Lease liabilities 11,584 9,683Current maturities of borrowings 22,217 38,025Liabilities to related parties 1,387 9,851Contract liabilities 16,024 59,183Taxes payable 1,106 925Other current liabilities 50,511 62,720Total current liabilities 160,549 260,950Total liabilities 1,576,655 1,882,583Total equity and liabilities 1,232,948 950,090 Unaudited Condensed Consolidated Interim Statements of Cash FlowsUSD thousandsCash flows from operating activitiesNine months ended30 September 2024Nine months ended30 September 2023Loss for the period (164,897) (275,174)Adjustments for non-cash items: Depreciation and amortization 23,14617,485Change in allowance for receivables — 18,500Change in inventory reserves (3,531) —Share-based payments 7,881 15,199Loss on disposal of property, plant and equipment 184 323Loss on sale of interest in joint venture 2,970 —Share of net loss of joint venture — 3,983Finance income (79,079) (46,383)Finance costs 237,683 107,826Exchange rate difference (1,657) (884)Loss on extinguishment of financial liabilities 69,378 —Income tax benefit (8,225) (67,076)Operating cash flow before movement in working capital 83,853 (226,201)Increase in inventories (47,050) (10,525)(Increase) / decrease in trade receivables (36,128) 11,027(Decrease) / increase in liabilities with related parties (8,367) 15(Increase) / decrease in contract assets (50,907) 2,031Increase in other assets (9,853) (15)Decrease in trade and other payables (27,937) (566)(Decrease) / increase in contract liabilities (30,474) 32,182Decrease in other liabilities (18,721) (21,737)Cash used in operations (145,584) (213,789)Interest received 97 46Interest paid (51,583) (30,582)Income tax paid (571) (697)Net cash used in operating activities (197,641) (245,022)Cash flows from investing activities Acquisition of property, plant and equipment (24,091) (29,440)Disposal of property, plant and equipment — 133Acquisition of intangible assets (1,857) (6,571)Restricted cash in connection with debt extinguishment 26,132 —Proceeds from the sale in joint venture 12,000 —Net cash generated from (used in) investing activities 12,184 (35,878)Cash flows from financing activities Repayments of borrowings (745,448) (97,538)Repayments of principal portion of lease liabilities (7,669) (5,838)Proceeds from new borrowings 900,805 244,908Transaction cost from new borrowings (4,236) —Gross proceeds from equity offering 150,451 136,877Fees from equity offering (5,812) (4,141)Proceeds from warrants 4,843 6,390Stock options exercised 76 —Net cash generated from financing activities 293,010 280,658Increase / (decrease) in cash and cash equivalents 107,553 (242)Cash and cash equivalents at the beginning of the year 11,157 66,427Effect of movements in exchange rates on cash held (436) 2,130Cash and cash equivalents at the end of the period 118,274 68,315 Attachment Presentation Q3 2024

Open a printable version of this page Email the URL of this page to a friend Get the RSS feed for this page Download a PDF version of this page Share this page on Twitter Share this page on LinkedIn Share this page on Facebook SPY001 was well tolerated with a favorable safety profile consistent with the anti-α4β7 class SPY001 pharmacokinetics exceeded expectations with a ~4-fold increase relative to vedolizumab, supporting potential Q6M maintenance dosing with a single subcutaneous (SC) injection Planned Phase 2 induction regimen targets drug concentrations in quartile 4 of vedolizumab's exposure-response relationship, which has the potential to increase or accelerate efficacy Single, lowest dose of SPY001 led to complete saturation of α4β7 receptors through Week 12 (longest follow-up available for pharmacodynamic data) Company plans to initiate a platform Phase 2 trial in mid-2025 that will include SPY001, followed by SPY002 (TL1A), SPY003 (IL-23), and combinations thereof, providing three optimized monotherapy readouts and three potentially paradigm-changing combination readouts under an efficient single master protocol Management will host a webcast and conference call today at 8:00 a.m. ET WALTHAM, Mass., Nov. 12, 2024 /PRNewswire/ -- Spyre Therapeutics, Inc. (NASDAQ: SYRE) (the "Company" or "Spyre"), a clinical-stage biotechnology company utilizing best-in-class antibody engineering, rational therapeutic combinations, and precision medicine approaches to target improved efficacy and convenience in the treatment of inflammatory bowel disease ("IBD"), today announced positive interim Phase 1 data from its first-in-human trial of SPY001, an investigational novel, extended half-life monoclonal antibody targeting α4β7. SPY001 was well tolerated with pharmacokinetic ("PK") data demonstrating a half-life of >90 days and pharmacodynamic ("PD") data demonstrating complete target engagement at all time points available. Interim results from the trial, with data as of October 30, 2024, exceeded the Company's expectations and support the potential for SPY001 to become a next-generation anti-α4β7 therapy and backbone for paradigm-changing combination therapies in IBD. The PK and PD results support optimized Phase 2 dosing including (i) increased induction exposures with the potential to improve or accelerate efficacy compared to other anti-α4β7 treatments and (ii) maintenance dosing on a potential Q3M and Q6M frequency via a single subcutaneous injection. Across single doses of up to 1000 mg and multiple doses of up to 600 mg, SPY001 was well-tolerated with no serious adverse events reported and all adverse events being mild in severity. Based on these data, and subject to regulatory feedback, the Company plans to initiate a Phase 2 platform trial in mid-2025 that will ultimately include SPY001, SPY002 (TL1A), SPY003 (IL-23) and combinations thereof, providing three optimized monotherapy readouts and three potentially paradigm-changing combination readouts under an efficient single master protocol. "These interim data exceeded our expectations for SPY001 and support its potential to become both a differentiated monotherapy and an ideal backbone for combination therapy in IBD," said Cameron Turtle, DPhil, Chief Executive Officer of Spyre. "We look forward to initiating Phase 2 trials next year that explore SPY001's safety and efficacy in IBD patients. Alongside our half-life-extended antibodies targeting TL1A and IL-23, we believe the Spyre portfolio is uniquely positioned to develop products that could substantially improve upon today's standard of care in IBD." Key SPY001 Phase 1 Interim Findings The SPY001 Phase 1 trial is a first-in-human, randomized, double-blind, placebo-controlled trial designed to evaluate safety and PK of SPY001 in healthy volunteers. To date, the trial has enrolled 56 healthy adult participants into five single-ascending dose (SAD) and two multiple-ascending dose (MAD) cohorts. Doses of SPY001 evaluated in the trial included single doses of 100 mg SC, 300 mg SC, 600 mg SC, 1,000 mg SC, and 1,000 mg IV and multiple doses of 300 mg SC and 600 mg IV. Findings from the interim SAD and MAD portions of the Phase 1 trial are as follows: Safety – well-tolerated across all dose groups Single doses of SPY001 up to 1,000 mg and multiple doses of 600 mg were well tolerated with a favorable safety profile consistent with existing third-party data of the anti-α4β7 class The most common (i.e., occurring in more than one subject) treatment-emergent adverse events ("TEAEs") were headache and nasopharyngitis. There were no Grade 2 or above TEAEs or serious adverse events ("SAEs"). No AEs led to trial discontinuation PK – meaningfully differentiated profile relative to vedolizumabHalf-life estimate is >90 days in the 300mg SC cohort and >100 days in the 600mg SC cohort, ~4-fold greater than vedolizumab's 25-day human half-lifeSPY001 half-life supports potential for maintenance dosing via a single subcutaneous injection on a Q3M and Q6M basis using a high-concentration, citrate-free formulation Dose-proportionality and limited intrasubject variability observed across key parameters (e.g., Cmax, AUC), support planned Phase 2 induction dosing to evaluate exposures of SPY001 in 4th quartile of vedolizumab's exposures to potentially achieve greater clinical remission rates and/or more rapid clinical effect No apparent impact of anti-drug antibodies observed on pharmacokinetic exposures PD – complete saturation of α4β7 receptor occupancy to latest time point availableSingle 300 mg dose of SPY001 saturated α4β7 receptor occupancy up to Day 57 (longest follow-up available with pharmacodynamic data) Exploratory immunophenotyping in progress, expected to be shared at upcoming academic conferences Spyre expects to share data from additional cohorts and longer follow-up from existing cohorts at future medical meetings. Platform Phase 2 trial in Ulcerative Colitis Pending regulatory feedback, Spyre plans to advance SPY001 into a double-blind, randomized, placebo-controlled, Phase 2 platform trial with a master protocol in patients with moderately-to-severely active ulcerative colitis. The platform trial is designed to efficiently evaluate each of Spyre's monotherapy and combination therapies against a common placebo control. The trial is also intended to evaluate the contribution of each monotherapy component to the safety and efficacy of Spyre's combination therapies. This Phase 2 ulcerative colitis trial is expected to initiate in mid-2025 with SPY001 and placebo arms, with SPY002, SPY003, and combination arms to be added following clinical data, nonclinical data, and regulatory feedback. The trial is expected to enroll approximately 500 subjects across treatment arms and consist of a 12-week, placebo-controlled induction period followed by a 38-week maintenance period. Updated portfolio guidance for maintenance dosing Given the PK results of SPY001, the Company is updating its guidance for maintenance dosing across the portfolio to Q3M-Q6M for monotherapies and combinations. Updated guidance highlights Spyre's unique ability to target a product profile with potentially best-in-indication efficacy and convenience. Conference Call and Webcast Spyre will host a conference call and webcast today, November 12, 2024, at 8:00 a.m. ET to discuss the SPY001 Phase 1 interim results. A live webcast of the call will be available on the Investor Relations website at https://ir.spyre.com/events-and-presentations. The webcast will be made available for replay on the company's website following completion of the event. About SPY001 SPY001 is an investigational novel, extended half-life monoclonal antibody targeting α4β7 for the potential treatment of IBD. IBD is a chronic condition characterized by inflammation in the gastrointestinal tract and encompasses two main disorders: ulcerative colitis and Crohn's disease. In the United States, it is estimated that approximately 2.4 million individuals currently have IBD. SPY001 targets the same epitope as vedolizumab and demonstrates equivalent potency and selectivity as vedolizumab in head-to-head preclinical studies. Interim data from a Phase 1 trial demonstrated that SPY001 was well tolerated and exhibited a human half-life of >90 days, a ~4-fold increase relative to vedolizumab. This half-life supports potential for both Q3M and Q6M SC maintenance dosing in a single autoinjector compared to vedolizumab's Q2W SC profile. Based on initial Phase 1 clinical data, the company plans to initiate a Phase 2 platform trial in ulcerative colitis in mid-2025. About Spyre Therapeutics Spyre Therapeutics is a clinical-stage biotechnology company that aims to create next-generation of inflammatory bowel disease (IBD) products by combining best-in-class antibody engineering, rational therapeutic combinations, and precision medicine approaches. Spyre's pipeline includes investigational extended half-life antibodies targeting α4β7, TL1A, and IL-23. For more information, please visit http://spyre.com. Forward-Looking Statements This press release contains "forward-looking" statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. All statements contained in this press release, other than statements of historical fact are forward-looking statements. These forward-looking statements include statements regarding the Company's business strategy, including the Company's ability to develop best-in-class therapeutics for IBD that meaningfully improve both efficacy and convenience compared to today's standard of care, the SPY001 phase 1 trial final data readout, the efficacy, safety and tolerability of SPY001 and its other product candidates, the planned induction and maintenance dosing regimen for SPY001 and its other product candidates, the potential for increased or accelerated efficacy, the therapeutic benefits of its product candidates as monotherapies or in combinations and their extended half-life, the expected design and timing of the platform Phase 2 trial, and that the human PK data is not based on head-to-head clinical trials and differences exist between trial design and patient populations which could confound the results. The words "believe," "may," "will," "potentially," "estimate," "continue," "anticipate," "predict," "target," "intend," "could," "would," "should," "project," "plan," "expect," the negatives of these terms, and similar expressions that convey uncertainty of future events or outcomes are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements involve a number of risks, uncertainties (some of which are beyond Spyre's control) or other assumptions that may cause actual results or performance, final clinical trial data readouts and clinically trial designs, including the planned Phase 2 trial to be materially different from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited to the final SPY001 Phase I trial data readouts not being consistent with or being different than the interim Phase I SPY001 results reported in this press release, regulatory feedback including potential disagreement by regulatory authorities with the Company's interpretation of data and the Company's planned clinical trials for its product candidates, including the Company's planned Phase 2 clinical trial design and those uncertainties and factors described under the heading "Risk Factors" and "Note about Forward-Looking Statements" in Spyre's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission, as well as discussions of potential risks, uncertainties, and other important factors included in other filings by Spyre from time to time. Should one or more of these risks or uncertainties materialize, or should any of Spyre's assumptions prove incorrect, actual results may vary in material respects from those projected in these forward-looking statements. Nothing in this press release should be regarded as a representation by any person that the forward-looking statements set forth therein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements in this press release, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. Spyre does not undertake or accept any duty to make any updates or revisions to any forward-looking statements. This press release does not purport to summarize all of the conditions, risks and other attributes of an investment in Spyre. SOURCE Spyre Therapeutics, Inc.