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More than two years of electronic medical records indicate patients were 89 percent more likely to start a next-line treatment when on acalabrutinib versus IMBRUVICA® NEW ORLEANS, Dec. 12, 2022 /PRNewswire/ --The Janssen Pharmaceutical Companies of Johnson & Johnson today announced results of a real-world study showing that patients with chronic lymphocytic leukemia (CLL) treated with first-line acalabrutinib monotherapy were 89 percent more likely to start a next-line treatment than those treated with IMBRUVICA® (ibrutinib).1 These data suggest the potential that first-line treatment with IMBRUVICA® in routine practice may provide patients with the ability to use once-daily, all-oral IMBRUVICA® as a monotherapy treatment for a longer period without the need to start the next line of therapy.1 Data from the study were featured in an oral presentation during the 2022 American Society of Hematology (ASH) Annual Meeting (Abstract #797). "There are currently no comparative clinical trials in first-line CLL among the BTKi class,1 highlighting the critical need to leverage real-world experience to support optimized treatment selection," said Ryan Jacobs†, M.D., Clinical Director, Division of Lymphoma Therapy & Research, Department of Hematologic Oncology, Atrium Health Levine Cancer Institute and principal study investigator. "These results demonstrate the possible impact of using ibrutinib versus acalabrutinib in the front-line setting and provide healthcare professionals with additional data showing differences in time to next treatment." The study used Acentrus‡, de-identified academic electronic medical records (EMR) to identify patients initiating first-line treatment with IMBRUVICA® or acalabrutinib between November 21, 2019 and April 30, 2022 and examined time to next treatment (TTNT) as a clinically meaningful surrogate measure for disease progression.1 TTNT was defined as the time from the index date to the initiation of a next or additional treatment.1 Results showed the following: Among treatment-naïve patients with CLL/small lymphocytic leukemia (SLL), patients treated with first-line acalabrutinib (n=373) were 89 percent more likely to start a next treatment than those treated with first-line IMBRUVICA® (n=710) (adjusted hazard ratio [HR] [95 percent confidence interval]: 1.89 (1.12, 3.13); P=0.016).1 A similar result was observed when censoring anti-CD20 add-on therapy any time after BTK inhibitor treatment (i.e., more than 180 days).1 At 12 months, 95.3 percent of patients treated with IMBRUVICA® had not initiated a next treatment versus 91.2 percent of patients treated with acalabrutinib.1 At 15 months, 94.6 percent of patients treated with IMBRUVICA® had not initiated next therapy versus 88.3 percent of patients treated with acalabrutinib.1 "Insights from real-world data are becoming more important to help physicians understand optimal treatments and sequencing, especially for patients living with chronic diseases like CLL," said Imran Khan, M.D., Ph. D., Vice President, Medical Affairs, Oncology, Janssen Biotech, Inc. "With nearly ten years of data since IMBRUVICA was first approved, we are sourcing real-world data to provide insights from large cohorts of patients further supporting IMBRUVICA as a first-line treatment option for CLL." Additional Study Details The Acentrus‡ database provides extensive information on medication orders, fills, and administrations. This enables the capture of oral medication use and is unique among available EMR datasets, including Flatiron.1 Patients were censored if another BTK inhibitor was initiated at any time, as this may be due to tolerability or non-medical switch rather than disease progression.1 Other criteria for censored patients were initiation of a second anti-cancer agent in addition to the index BTK inhibitor treatment within 180 days post-index, as this may indicate a first-line combination treatment strategy.1 The addition of an anti-CD20 antibody or venetoclax after 180 days were considered next treatments.1 Patients without a next or additional treatment were censored at death or end of data entries.1 The median age of patients treated with IMBRUVICA® and acalabrutinib were similar (IMBRUVICA® 73 years [n=710]; acalabrutinib 72 years [n=373]).1 Real-World Data Limitations Real world data have the potential to supplement controlled trial data by providing additional information about how a medicine performs across clinical trials and in routine clinical practice. There are limitations, however, and these data cannot be used as stand-alone evidence to validate the efficacy or safety of a treatment. Limitations exist based on EMR data, including potential omissions.1 However, these would be at random and are expected to have minimal impact on results.1 Further research is warranted with additional follow-up and larger sample size to inform the evidence gap on the comparative effectiveness of newer BTK inhibitors.1 About IMBRUVICA® IMB­RUVICA® (ibrutinib) is a once-daily oral medication that is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company. IMBRUVICA® blocks the Bruton's tyrosine kinase (BTK) protein, which is needed by normal and abnormal B cells, including specific cancer cells, to multiply and spread. By blocking BTK, IMBRUVICA® may help move abnormal B cells out of their nourishing environments and inhibits their proliferation.2,3,4 IMBRUVICA® is approved in more than 100 countries and has been used to treat more than 270,000 patients worldwide. There are more than 50 company-sponsored clinical trials, including 18 Phase 3 studies, more than 11 years evaluating the efficacy and safety of IMBRUVICA®. IMBRUVICA® was first approved by the U.S. Food and Drug Administration (FDA) in November 2013 and today is indicated for adult patients in six disease areas, including five hematologic cancers. These include indications to treat adults with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with or without 17p deletion (del17p), adults with Waldenström's macroglobulinemia (WM), adult patients with previously treated mantle cell lymphoma (MCL)*, as well as to treat adult patients with previously treated marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy*, and adult and pediatric patients aged one year and older with previously treated chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.5 *Accelerated approval was granted for MCL and MZL based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials. For more information, visit . IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Hemorrhage: Fatal bleeding events have occurred in patients who received IMBRUVICA®. Major hemorrhage (≥ Grade 3, serious, or any central nervous system events; e.g., intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post procedural hemorrhage) occurred in 4.2% of patients, with fatalities occurring in 0.4% of 2,838 patients who received IMBRUVICA® in 27 clinical trials. Bleeding events of any grade including bruising and petechiae occurred in 39% and excluding bruising and petechiae occurred in 23% of patients who received IMBRUVICA®, respectively. The mechanism for the bleeding events is not well understood. Use of either anticoagulant or antiplatelet agents concomitantly with IMBRUVICA® increases the risk of major hemorrhage. Across clinical trials, 3.1% of 2,838 patients who received IMBRUVICA® without antiplatelet or anticoagulant therapy experienced major hemorrhage. The addition of antiplatelet therapy with or without anticoagulant therapy increased this percentage to 4.4 percent, and the addition of anticoagulant therapy with or without antiplatelet therapy increased this percentage to 6.1%. Consider the risks and benefits of anticoagulant or antiplatelet therapy when co-administered with IMBRUVICA®. Monitor for signs and symptoms of bleeding. Consider the benefit-risk of withholding IMBRUVICA® for at least 3 to 7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding. Infections: Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with IMBRUVICA® therapy. Grade 3 or greater infections occurred in 21% of 1,476 patients who received IMBRUVICA® in clinical trials. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA®. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections. Monitor and evaluate patients for fever and infections and treat appropriately. Cardiac Arrhythmias, Cardiac Failure, and Sudden Death: Fatal and serious cardiac arrhythmias and cardiac failure have occurred with IMBRUVICA®. Deaths due to cardiac causes or sudden deaths occurred in 1% of 4,896 patients who received IMBRUVICA® in clinical trials, including in patients who received IMBRUVICA® in unapproved monotherapy or combination regimens. These adverse reactions occurred in patients with and without preexisting hypertension or cardiac comorbidities. Patients with cardiac comorbidities may be at greater risk of these events. Grade 3 or greater ventricular tachyarrhythmias were reported in 0.2%, Grade 3 or greater atrial fibrillation and atrial flutter were reported in 3.7%, and Grade 3 or greater cardiac failure was reported in 1.3% of 4,896 patients who received IMBRUVICA® in clinical trials, including in patients who received IMBRUVICA® in unapproved monotherapy or combination regimens. These events have occurred particularly in patients with cardiac risk factors including hypertension and diabetes mellitus, a previous history of cardiac arrhythmias, and in patients with acute infections. Evaluate cardiac history and function at baseline, and monitor patients for cardiac arrhythmias and cardiac function. Obtain further evaluation (e.g., ECG, echocardiogram) as indicated for patients who develop symptoms of arrhythmia (e.g., palpitations, lightheadedness, syncope, chest pain), new onset dyspnea, or other cardiovascular concerns. Manage cardiac arrhythmias and cardiac failure appropriately, follow dose modification guidelines, and consider the risks and benefits of continued IMBRUVICA® treatment. Hypertension: Hypertension occurred in 19% of 1,476 patients who received IMBRUVICA® in clinical trials. Grade 3 or greater hypertension occurred in 8% of patients. Based on data from 1,124 of these patients, the median time to onset was 5.9 months (range, 0.03 to 24 months). Monitor blood pressure in patients treated with IMBRUVICA®, initiate or adjust anti-hypertensive medication throughout treatment with IMBRUVICA® as appropriate, and follow dosage modification guidelines for Grade 3 or higher hypertension. Cytopenias: In 645 patients with B-cell malignancies who received IMBRUVICA® as a single agent, grade 3 or 4 neutropenia occurred in 23% of patients, grade 3 or 4 thrombocytopenia in 8% and grade 3 or 4 anemia in 2.8%, based on laboratory measurements. Monitor complete blood counts monthly. Second Primary Malignancies: Other malignancies (10%), including non-skin carcinomas (3.9%), occurred among the 1,476 patients who received IMBRUVICA® in clinical trials. The most frequent second primary malignancy was non-melanoma skin cancer (6%). Tumor Lysis Syndrome: Tumor lysis syndrome has been infrequently reported with IMBRUVICA®. Assess the baseline risk (e.g., high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate. Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA® can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMBRUVICA® and for 1 month after the last dose. Advise males with female partners of reproductive potential to use effective contraception during the same time period. ADVERSE REACTIONS B-cell malignancies: The most common adverse reactions (≥30%) in adult patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were thrombocytopenia (54.5%)*, diarrhea (43.8%), fatigue (39.1%), musculoskeletal pain (38.8%), neutropenia (38.6%)*, rash (35.8%), anemia (35.0%)*, and bruising (32.0%). The most common Grade ≥ 3 adverse reactions (≥5%) in adult patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia (20.7%)*, thrombocytopenia (13.6%)*, pneumonia (8.2%), and hypertension (8.0%). Approximately 9% (CLL/SLL), 14% (MCL), 14% (WM) and 10% (MZL) of adult patients had a dose reduction due to adverse reactions. Approximately 4-10% (CLL/SLL), 9% (MCL), and 7% (WM [5%] and MZL [13%]) of patients discontinued due to adverse reactions. cGVHD: The most common adverse reactions (≥20%) in adult or pediatric patients with cGVHD were fatigue (57%), anemia (49%)*, bruising (40%), diarrhea (36%), thrombocytopenia (33%)*, musculoskeletal pain (30%), pyrexia (30%), muscle spasms (29%), stomatitis (29%), hemorrhage (26%), nausea (26%), abdominal pain (23%), pneumonia (23%), and headache (21%). The most common Grade 3 or higher adverse reactions (≥5%) reported in adult or pediatric patients with cGVHD were pneumonia (14%), anemia (13%)*, fatigue (12%), pyrexia (11%), diarrhea (10%), neutropenia (10%)*, sepsis (10%), osteonecrosis (9%), stomatitis (9%), hypokalemia (7%), headache (5%), and musculoskeletal pain (5%). Discontinuation of IMBRUVICA® treatment due to an adverse reaction occurred in 24% of adult patients and 23% of pediatric patients. Adverse reactions leading to dose reduction occurred in 26% of adult patients and 19% of pediatric patients. *Treatment-emergent decreases (all grades) were based on laboratory measurements. DRUG INTERACTIONS CYP3A Inhibitors: Co-administration of IMBRUVICA® with strong or moderate CYP3A inhibitors may increase ibrutinib plasma concentrations. Increased ibrutinib concentrations may increase the risk of drug-related toxicity. Dose modifications of IMBRUVICA® are recommended when used concomitantly with posaconazole, voriconazole, and moderate CYP3A inhibitors. Avoid concomitant use of other strong CYP3A inhibitors. Interrupt IMBRUVICA® if strong inhibitors are used short-term (e.g., for ≤ 7 days). Avoid grapefruit and Seville oranges during IMBRUVICA® treatment, as these contain strong or moderate inhibitors of CYP3A. See dose modification guidelines in USPI sections 2.3 and 7.1. CYP3A Inducers: Avoid coadministration with strong CYP3A inducers. SPECIFIC POPULATIONS Pediatric Use: The safety and effectiveness of IMBRUVICA® have not been established for the treatment of cGVHD after failure of one or more lines of therapy in pediatric patients less than 1 year of age. The safety and effectiveness of IMBRUVICA® in pediatric patients have not been established in MCL, CLL/SLL, CLL/SLL with 17p deletion, WM, MZL or in patients with mature B-cell non-Hodgkin lymphoma. In the randomized population from a study that included 35 patients (26 pediatric patients age 5 to less than 17 years) with previously treated mature B-cell non-Hodgkin lymphoma, major hemorrhage and discontinuation of chemoimmunotherapy due to adverse reactions occurred more frequently in the ibrutinib plus chemoimmunotherapy arm compared to the chemoimmunotherapy alone arm. Hepatic Impairment: Adult Patients with B-cell Malignancies: Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA® in patients with severe hepatic impairment. In patients with mild or moderate impairment, reduce recommended IMBRUVICA® dose and monitor more frequently for adverse reactions of IMBRUVICA®. Patients with cGVHD: Avoid use of IMBRUVICA® in patients with total bilirubin level > 3x upper limit of normal (ULN) (unless of non-hepatic origin or due to Gilbert's syndrome). Reduce recommended dose when administering IMBRUVICA® to patients with total bilirubin level > 1.5 to 3x ULN (unless of non-hepatic origin or due to Gilbert's syndrome). Please click here to see the full Prescribing Information About the Janssen Pharmaceutical Companies of Johnson & Johnson At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension. Learn more at . Follow us at @JanssenGlobal and @JanssenUS. Janssen Biotech, Inc. is one of the Janssen Pharmaceutical Companies of Johnson & Johnson. †Dr. Jacobs has served as a consultant to Janssen; he has not been paid for any media work. ‡ Acentrus is a health system solution utilized by 128,000 prescribers/physicians containing in-patient and out-patient data from 27 sites, including 10 NCI-designated sites and 6 NCCN network members, across 15 US states. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of IMBRUVICA® (ibrutinib). The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC or any of the other Janssen Pharmaceutical Companies, and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 2, 2022, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Reports on Form 10-Q, and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. 1 Jacobs R., et al. Real-World Comparison of Time to Next Treatment for Patients with CLL Initiated on First-line Treatment with Ibrutinib versus Acalabrutinib. 2022 American Society of Hematology Annual Meeting. December 12, 2022. 2 Genetics Home Reference. Isolated growth hormone deficiency. . 3 Turetsky A, et al. Single cell imaging of Bruton's tyrosine kinase using an irreversible inhibitor. Scientific Reports. 2014;6:4782. 4 de Rooij MF, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012;119(11):2590-2594. 5 IMBRUVICA® U.S. Prescribing Information, August 2022. Media Inquiries: Jessica Castles Smith (732) 501-8181 Christie Corbett (857) 636-0211 Investor Relations: Raychel Kruper (732) 524-6164 U.S. Medical Inquiries: +1 800-526-7736

New Orders Contracting; Production Growing; Backlogs Contracting; Supplier Deliveries Faster; Raw Materials Inventories Growing; Customers' Inventories Too Low; Prices Decreasing; Exports and Imports Contracting TEMPE, Ariz., Dec. 1, 2022 /PRNewswire/ -- Economic activity in the manufacturing sector contracted in November for the first time since May 2020 after 29 consecutive months of growth, say the nation's supply executives in the latest Manufacturing ISM® Report On Business®. The report was issued today by Timothy R. Fiore, CPSM, C.P.M., Chair of the Institute for Supply Management® (ISM®) Manufacturing Business Survey Committee: "The November Manufacturing PMI® registered 49 percent, 1.2 percentage points lower than the 50.2 percent recorded in October. Regarding the overall economy, this figure indicates expansion for the 30th month in a row after contraction in April and May 2020. The Manufacturing PMI® figure is the lowest since May 2020, when it registered 43.5 percent. The New Orders Index remained in contraction territory at 47.2 percent, 2 percentage points lower than the 49.2 percent recorded in October. The Production Index reading of 51.5 percent is a 0.8-percentage point decrease compared to October's figure of 52.3 percent. The Prices Index registered 43 percent, down 3.6 percentage points compared to the October figure of 46.6 percent; this is the index's lowest reading since May 2020 (40.8 percent). The Backlog of Orders Index registered 40 percent, 5.3 percentage points lower than the October reading of 45.3 percent. The Employment Index returned to contraction territory (48.4 percent, down 1.6 percentage points) after being unchanged in October at 50 percent. The Supplier Deliveries Index reading of 47.2 percent is 0.4 percentage point higher than the October figure of 46.8 percent. Except for last month, the Supplier Deliveries Index hasn't been at this level since February 2012 (47 percent). The Inventories Index registered 50.9 percent, 1.6 percentage points lower than the October reading of 52.5 percent. The New Export Orders Index reading of 48.4 percent is up 1.9 percentage points compared to October's figure of 46.5 percent. The Imports Index dropped into contraction territory at 46.6 percent, 4.2 percentage points below the October reading of 50.8 percent." Fiore continues, "The U.S. manufacturing sector dipped into contraction, with the Manufacturing PMI® at its lowest level since the coronavirus pandemic recovery began. With Business Survey Committee panelists reporting softening new order rates over the previous six months, the November composite index reading reflects companies' preparing for future lower output . Demand eased, with the (1) New Orders Index remaining in contraction territory, (2) New Export Orders Index below 50 percent for a fourth consecutive month, (3) Customers' Inventories Index effectively in 'just right' territory, climbing 7.1 percentage points, and (4) Backlog of Orders Index moving deeper into contraction. Output/Consumption (measured by the Production and Employment indexes) declined month over month, with a combined negative 2.4-percentage point impact on the Manufacturing PMI® calculation. The Employment Index moved back into contraction, and the Production Index decreased but still remained in modest growth territory. Panelists' companies confirm that they are continuing to manage head counts through a combination of hiring freezes, employee attrition, and now layoffs. Inputs — defined as supplier deliveries, inventories, prices and imports — mostly accommodated future demand growth. The Supplier Deliveries Index indicated faster deliveries, and the Inventories Index expanded at a slower rate as panelists' companies continued to manage the total supply chain inventory. The Prices Index decreased for the ninth consecutive month, falling deeper into contraction territory. "Of the six biggest manufacturing industries, two — Petroleum & Coal Products; and Transportation Equipment — registered weak-to-moderate growth in November. "Manufacturing contracted in November after expanding for 29 straight months. Panelists' companies continue to judiciously manage hiring, other than October 2022, the month-over-month supplier delivery performance was the best since February 2012 when it registered 47 percent, and material lead times declined approximately 9 percent from the prior month, approximately 18 percent over the last four months. Managing head counts and total supply chain inventories remain primary goals. Order backlogs, prices and now lead times are declining rapidly, which should bring buyers and sellers back to the table to refill order books based on 2023 business plans." Six manufacturing industries reported growth in November, in the following order: Apparel, Leather & Allied Products; Nonmetallic Mineral Products; Primary Metals; Miscellaneous Manufacturing; Petroleum & Coal Products; and Transportation Equipment. The 12 industries reporting contraction in November, in the following order, are: Printing & Related Support Activities; Wood Products; Paper Products; Textile Mills; Fabricated Metal Products; Furniture & Related Products; Chemical Products; Plastics & Rubber Products; Computer & Electronic Products; Food, Beverage & Tobacco Products; Machinery; and Electrical Equipment, Appliances & Components. WHAT RESPONDENTS ARE SAYING "Customer demand is softening, yet suppliers are maintaining high prices and record profits. Pushing for cost reductions based on market evidence has been surprisingly successful." [Computer & Electronic Products] "Future volumes are on a downward trend for the next 60 days." [Chemical Products] "Orders for transportation equipment remain strong. Supply chain issues persist, with minimal direct effect on output." [Transportation Equipment] "Consumer goods are slowing down in several of our markets, although the U.S. economy seems decent. Cannot say the same for the European economy." [Food, Beverage & Tobacco Products] "General economic uncertainty has created a slowdown in orders as we approach the end of the year, and many of our key customers are reducing their capital expenditures spend." [Machinery] "Overall, things are worsening. Housing starts are down. We're doing well against our competitors, but the industry overall is down. We're sitting on cash (that is) tied up in inventory." [Electrical Equipment, Appliances & Components] "The market remains consistent: sales match expectations; there are concerns about the impact of rising interest rates on customers; most suppliers have recovered on labor, but some are still struggling; and inflation seems to have peaked, but commodity price decreases have not been passed through to us. Lots of unknowns regarding impact to the European Union from the Russia-Ukraine war and questions about customer behavior in 2023." [Miscellaneous Manufacturing] "There is caution going into 2023, but the commercial section of construction seems to still be going strong." [Nonmetallic Mineral Products] "Looking into December and the first quarter of 2023, business is softening as uncertain economic conditions lie ahead." [Plastics & Rubber Products] "Slight improvement on overall business conditions from the previous month." [Primary Metals] Manufacturing ISM ® Report On Business® data is seasonally adjusted for the New Orders, Production, Employment and Inventories indexes. *Number of months moving in current direction. COMMODITIES REPORTED UP/DOWN IN PRICE AND IN SHORT SUPPLY Commodities Up in Price Electrical Components; Electricity; Electronic Components (24); and Labor — Temporary (3). Commodities Down in Price Aluminum (7); Copper (2); Freight; Lumber (3); Ocean Freight (3); Plastic Resins (6); Polypropylene (4); Steel (7); Steel — Carbon (5); Steel — Hot Rolled (7); and Steel Products (5). Commodities in Short Supply Electrical Components (26); Electronic Components (24); Hydraulic Components (7); Rubber Based Products; Semiconductors (24); and Steel Products. Note: The number of consecutive months the commodity is listed is indicated after each item. NOVEMBER 2022 MANUFACTURING INDEX SUMMARIES Manufacturing PMI® The U.S. manufacturing sector contracted in November, as the Manufacturing PMI® registered 49 percent, 1.2 percentage points below the reading of 50.2 percent recorded in October. "After five months of flat or marginally positive change, the decrease last month took the Manufacturing PMI® into contraction. Of the five subindexes that directly factor into the Manufacturing PMI®, two (Production and Inventories) were in growth territory, though both eased. The PMI® registered its lowest level since May 2020, when the index was 43.5 percent. Of the six biggest manufacturing industries, two — Petroleum & Coal Products; and Transportation Equipment — registered weak-to-moderate growth in November. The Production Index decreased 0.8 percentage point, inching closer to contraction territory. Supply chain congestion continued to ease, indicated by the Supplier Deliveries Index showing faster deliveries. Only two of the 10 subindexes were positive for the period," says Fiore. A reading above 50 percent indicates that the manufacturing sector is generally expanding; below 50 percent indicates that it is generally contracting. A Manufacturing PMI® above 48.7 percent, over a period of time, generally indicates an expansion of the overall economy. Therefore, the November Manufacturing PMI® indicates the overall economy grew in November for the 30th consecutive month following contraction in April and May 2020. "The past relationship between the Manufacturing PMI® and the overall economy indicates that the Manufacturing PMI® for November (49 percent) corresponds to a 0.1-percent increase in real gross domestic product (GDP) on an annualized basis," says Fiore. THE LAST 12 MONTHS New Orders ISM®'s New Orders Index contracted for the third consecutive month in November, registering 47.2 percent, a decrease of 2 percentage points compared to the 49.2 percent reported in October. "None of the six largest manufacturing sectors reported increased new orders. Price and lead time declines as well as backlog contraction should encourage buyers to reenter the market and sales agents to be more aggressive in seeking new business," says Fiore. (For more on lead times, see the Buying Policy section of this report.) A New Orders Index above 52.9 percent, over time, is generally consistent with an increase in the Census Bureau's series on manufacturing orders (in constant 2000 dollars). Of the 18 manufacturing industries, only one reported growth in new orders in November: Apparel, Leather & Allied Products. Fourteen industries reported a decline in new orders in November, in the following order: Wood Products; Printing & Related Support Activities; Paper Products; Primary Metals; Nonmetallic Mineral Products; Electrical Equipment, Appliances & Components; Fabricated Metal Products; Machinery; Plastics & Rubber Products; Chemical Products; Transportation Equipment; Miscellaneous Manufacturing; Food, Beverage & Tobacco Products; and Computer & Electronic Products. Production The Production Index registered 51.5 percent in November, 0.8 percentage point lower than the October reading of 52.3 percent, indicating growth for the 30th consecutive month. "Of the top six industries, only two — Computer & Electronic Products; and Transportation Equipment — expanded in November. Materials and labor availability continue to improve, as panelists' companies begin to significantly reduce their backlogs of overdue orders," says Fiore. An index above 52.4 percent, over time, is generally consistent with an increase in the Federal Reserve Board's Industrial Production figures. The seven industries reporting growth in production during the month of November — listed in order — are: Apparel, Leather & Allied Products; Primary Metals; Nonmetallic Mineral Products; Computer & Electronic Products; Plastics & Rubber Products; Transportation Equipment; and Electrical Equipment, Appliances & Components. The seven industries reporting a decrease in production in November — in the following order — are: Printing & Related Support Activities; Textile Mills; Furniture & Related Products; Machinery; Food, Beverage & Tobacco Products; Miscellaneous Manufacturing; and Fabricated Metal Products. Employment ISM®'s Employment Index registered 48.4 percent in November, 1.6 percentage points lower than the October reading of 50 percent. "The index indicated employment contracted after being unchanged for one month. Of the six big manufacturing sectors, only two (Food, Beverage & Tobacco Products; and Machinery) expanded. Labor management sentiment continued to shift, with a number of panelists' companies reducing employment levels through hiring freezes, attrition, and now layoffs. In November, layoffs were mentioned in 14 percent of employment comments, up from 6 percent in October. Turnover rates remained consistent, with 30 percent of comments citing backfill and retirement issues, generally the same rate since September. For those companies expanding their workforces, comments continue to support an improving hiring environment," says Fiore. An Employment Index above 50.5 percent, over time, is generally consistent with an increase in the Bureau of Labor Statistics (BLS) data on manufacturing employment. Of 18 manufacturing industries, seven reported employment growth in November, in the following order: Apparel, Leather & Allied Products; Primary Metals; Miscellaneous Manufacturing; Electrical Equipment, Appliances & Components; Plastics & Rubber Products; Food, Beverage & Tobacco Products; and Machinery. The five industries reporting a decrease in employment in November are: Textile Mills; Paper Products; Computer & Electronic Products; Chemical Products; and Fabricated Metal Products. Six industries reported no change in employment in November compared to October. Supplier Deliveries† The delivery performance of suppliers to manufacturing organizations was faster for a second straight month in November, as the Supplier Deliveries Index registered 47.2 percent, 0.4 percentage point higher than the 46.8 percent reported in October. Prior to October, the last reading under 50 percent was in February 2016 (49.6 percent); this is the first time the index has spent consecutive months in "faster" territory since October-December 2015. Of the top six manufacturing industries, one (Petroleum & Coal Products) reported slower deliveries. "Although a touch slower than the previous month, the November reading indicates the best month-over-month supplier deliveries performance in more than a decade (since February 2012, when the index registered 47 percent). In November, 86.1 percent of panelists reported 'same' or 'faster' delivery times. Panelists' comments overwhelmingly confirmed that suppliers performed better in November compared to previous months," says Fiore. A reading below 50 percent indicates faster deliveries, while a reading above 50 percent indicates slower deliveries. Six of 18 manufacturing industries reported slower supplier deliveries in November, in the following order: Apparel, Leather & Allied Products; Textile Mills; Petroleum & Coal Products; Nonmetallic Mineral Products; Primary Metals; and Miscellaneous Manufacturing. The 11 industries reporting faster supplier deliveries in November as compared to October — in the following order — are: Wood Products; Electrical Equipment, Appliances & Components; Paper Products; Plastics & Rubber Products; Furniture & Related Products; Fabricated Metal Products; Chemical Products; Computer & Electronic Products; Machinery; Food, Beverage & Tobacco Products; and Transportation Equipment. Inventories The Inventories Index registered 50.9 percent in November, 1.6 percentage points lower than the 52.5 percent reported for October. "Manufacturing inventories expanded at a slower rate compared to October. The index recorded its lowest level since July 2021, when it registered 49.1 percent. Of the six big manufacturing industries, four (Machinery; Computer & Electronic Products; Transportation Equipment; and Chemical Products) increased manufacturing raw material inventories in November. Panelists' companies continue their efforts to reduce their total supply chain inventories, indicated by the contraction in new orders, slow expansion in manufacturing inventories and the 'just right' level of customers' inventories," says Fiore. An Inventories Index greater than 44.4 percent, over time, is generally consistent with expansion in the Bureau of Economic Analysis (BEA) figures on overall manufacturing inventories (in chained 2000 dollars). Of 18 manufacturing industries, the eight reporting higher inventories in November — in the following order — are: Nonmetallic Mineral Products; Electrical Equipment, Appliances & Components; Miscellaneous Manufacturing; Primary Metals; Machinery; Computer & Electronic Products; Transportation Equipment; and Chemical Products. The eight industries reporting contracting inventories in November — in the following order — are: Printing & Related Support Activities; Wood Products; Textile Mills; Apparel, Leather & Allied Products; Paper Products; Fabricated Metal Products; Petroleum & Coal Products; and Plastics & Rubber Products. Customers' Inventories† ISM®'s Customers' Inventories Index registered 48.7 percent in November, 7.1 percentage points higher than the 41.6 percent reported for October. "Customers' inventory levels are considered essentially 'just right.' The index recorded its highest level since April 2020 (48.8 percent). The current index level is no longer providing positive support to future manufacturing expansion," says Fiore. Six industries reported customers' inventories as too high in November, in the following order: Textile Mills; Paper Products; Wood Products; Primary Metals; Chemical Products; and Electrical Equipment, Appliances & Components. The eight industries reporting customers' inventories as too low in November — listed in order — are: Nonmetallic Mineral Products; Machinery; Petroleum & Coal Products; Miscellaneous Manufacturing; Transportation Equipment; Food, Beverage & Tobacco Products; Computer & Electronic Products; and Fabricated Metal Products. Prices † The ISM® Prices Index registered 43 percent in November, 3.6 percentage points lower compared to the October reading of 46.6 percent, indicating raw materials prices decreased for the second time in 29 months. This is the index's lowest level since a reading of 40.8 percent in May 2020. Over the past eight months, the index has decreased 44.1 percentage points, including a combined 26-percentage point plunge in July and August. None of the top six manufacturing industries reported increases in prices in November. "Price declines continue to be driven by relaxation in energy markets, copper, steel, aluminum, plastics, corrugate and as well as volatility in freight costs. Notably, 87 percent of respondents reported paying the same or lower prices in November, compared to 80 percent in October," says Fiore. A Prices Index above 52.6 percent, over time, is generally consistent with an increase in the Bureau of Labor Statistics (BLS) Producer Price Index for Intermediate Materials. In November, only one industry reported paying increased prices for raw materials: Miscellaneous Manufacturing. The 10 industries reporting paying decreased prices for raw materials in November — in the following order — are: Textile Mills; Wood Products; Furniture & Related Products; Fabricated Metal Products; Plastics & Rubber Products; Transportation Equipment; Chemical Products; Electrical Equipment, Appliances & Components; Machinery; and Computer & Electronic Products. Seven industries reported no change in prices in November compared to October. Backlog of Orders† ISM®'s Backlog of Orders Index registered 40 percent in November, a 5.3-percentage point decrease compared to October's reading of 45.3 percent, indicating order backlogs contracted for the second consecutive month after a 27-month period of expansion. Of the six largest manufacturing sectors, only one — Machinery — expanded order backlogs in November. "Backlogs contracted again in November at a notable rate, as weak new order levels combined with production expansion negatively impacted manufacturing books of business," says Fiore. "The index recorded its lowest level since May 2020, when it registered 38.2 percent." Two industries reported growth in order backlogs in November: Apparel, Leather & Allied Products; and Machinery. Twelve industries reported lower backlogs in November, in the following order: Wood Products; Textile Mills; Printing & Related Support Activities; Paper Products; Primary Metals; Furniture & Related Products; Chemical Products; Plastics & Rubber Products; Computer & Electronic Products; Electrical Equipment, Appliances & Components; Transportation Equipment; and Fabricated Metal Products. New Export Orders† ISM®'s New Export Orders Index registered 48.4 percent in November, 1.9 percentage points higher than the October reading of 46.5 percent. "The New Export Orders Index contracted in November for the fourth consecutive month after 25 straight months in expansion territory. Weakness in European economies and China's economic sluggishness, as well as the strong dollar, continued to constrain new export order activity and negatively impact new order rates," says Fiore. Three industries reported growth in new export orders in November: Nonmetallic Mineral Products; Plastics & Rubber Products; and Food, Beverage & Tobacco Products. The four industries reporting a decrease in new export orders in November are: Fabricated Metal Products; Chemical Products; Machinery; and Computer & Electronic Products. Ten industries reported no change in new export orders in November compared to October. Imports† ISM®'s Imports Index registered 46.6 percent in November, a decrease of 4.2 percentage points compared to October's figure of 50.8 percent. "The index moved into contraction in November after five months of expansion, dropping to its lowest level since May 2020 (41.3 percent)," says Fiore. The four industries reporting growth in imports in November are: Apparel, Leather & Allied Products; Computer & Electronic Products; Miscellaneous Manufacturing; and Transportation Equipment. Nine industries reported lower volumes of imports in November, in the following order: Wood Products; Paper Products; Petroleum & Coal Products; Nonmetallic Mineral Products; Chemical Products; Fabricated Metal Products; Electrical Equipment, Appliances & Components; Machinery; and Food, Beverage & Tobacco Products. †The Supplier Deliveries, Customers' Inventories, Prices, Backlog of Orders, New Export Orders, and Imports indexes do not meet the accepted criteria for seasonal adjustments. Buying Policy The average commitment lead time for Capital Expenditures in November was 177 days, a decrease of two days compared to October. Average lead time in November for Production Materials was 84 days, a decrease of nine days. Average lead time for Maintenance, Repair and Operating (MRO) Supplies was 44 days, a decrease of four days. About This Report DO NOT CONFUSE THIS NATIONAL REPORT with the various regional purchasing reports released across the country. The national report's information reflects the entire U.S., while the regional reports contain primarily regional data from their local vicinities. Also, the information in the regional reports is not used in calculating the results of the national report. The information compiled in this report is for the month of November 2022. The data presented herein is obtained from a survey of manufacturing supply executives based on information they have collected within their respective organizations. ISM® makes no representation, other than that stated within this release, regarding the individual company data collection procedures. The data should be compared to all other economic data sources when used in decision-making. Data and Method of Presentation The Manufacturing ISM® Report On Business® is based on data compiled from purchasing and supply executives nationwide. The composition of the Manufacturing Business Survey Committee is stratified according to the North American Industry Classification System (NAICS) and each of the following NAICS-based industry's contribution to gross domestic product (GDP): Food, Beverage & Tobacco Products; Textile Mills; Apparel, Leather & Allied Products; Wood Products; Paper Products; Printing & Related Support Activities; Petroleum & Coal Products; Chemical Products; Plastics & Rubber Products; Nonmetallic Mineral Products; Primary Metals; Fabricated Metal Products; Machinery; Computer & Electronic Products; Electrical Equipment, Appliances & Components; Transportation Equipment; Furniture & Related Products; and Miscellaneous Manufacturing (products such as medical equipment and supplies, jewelry, sporting goods, toys and office supplies). The data are weighted based on each industry's contribution to GDP. According to the BEA estimates for 2020 GDP (released December 22, 2021), the six largest manufacturing subsectors are: Computer & Electronic Products; Chemical Products; Transportation Equipment; Petroleum & Coal Products; Food, Beverage & Tobacco Products; and Machinery. Beginning in February 2018 with January 2018 data, computation of the indexes is accomplished utilizing unrounded numbers. Survey responses reflect the change, if any, in the current month compared to the previous month. For each of the indicators measured (New Orders, Backlog of Orders, New Export Orders, Imports, Production, Supplier Deliveries, Inventories, Customers' Inventories, Employment and Prices), this report shows the percentage reporting each response, the net difference between the number of responses in the positive economic direction (higher, better and slower for Supplier Deliveries) and the negative economic direction (lower, worse and faster for Supplier Deliveries), and the diffusion index. Responses are raw data and are never changed. The diffusion index includes the percent of positive responses plus one-half of those responding the same (considered positive). The resulting single index number for those meeting the criteria for seasonal adjustments (Manufacturing PMI®, New Orders, Production, Employment and Inventories) is then seasonally adjusted to allow for the effects of repetitive intra-year variations resulting primarily from normal differences in weather conditions, various institutional arrangements, and differences attributable to non-moveable holidays. All seasonal adjustment factors are subject annually to relatively minor changes when conditions warrant them. The Manufacturing PMI® is a composite index based on the diffusion indexes of five of the indexes with equal weights: New Orders (seasonally adjusted), Production (seasonally adjusted), Employment (seasonally adjusted), Supplier Deliveries, and Inventories (seasonally adjusted). Diffusion indexes have the properties of leading indicators and are convenient summary measures showing the prevailing direction of change and the scope of change. A Manufacturing PMI® reading above 50 percent indicates that the manufacturing economy is generally expanding; below 50 percent indicates that it is generally declining. A Manufacturing PMI® above 48.7 percent, over a period of time, indicates that the overall economy, or gross domestic product (GDP), is generally expanding; below 48.7 percent, it is generally declining. The distance from 50 percent or 48.7 percent is indicative of the extent of the expansion or decline. With some of the indicators within this report, ISM® has indicated the departure point between expansion and decline of comparable government series, as determined by regression analysis. The Manufacturing ISM® Report On Business® survey is sent out to Manufacturing Business Survey Committee respondents the first part of each month. Respondents are asked to report on information for the current month for U.S. operations only. ISM® receives survey responses throughout most of any given month, with the majority of respondents generally waiting until late in the month to submit responses to give the most accurate picture of current business activity. ISM® then compiles the report for release on the first business day of the following month. The industries reporting growth, as indicated in the Manufacturing ISM® Report On Business® monthly report, are listed in the order of most growth to least growth. For the industries reporting contraction or decreases, those are listed in the order of the highest level of contraction/decrease to the least level of contraction/decrease. Responses to Buying Policy reflect the percent reporting the current month's lead time, the approximate weighted number of days ahead for which commitments are made for Capital Expenditures; Production Materials; and Maintenance, Repair and Operating (MRO) Supplies, expressed as hand-to-mouth (five days), 30 days, 60 days, 90 days, six months (180 days), a year or more (360 days), and the weighted average number of days. These responses are raw data, never revised, and not seasonally adjusted. ISM ROB Content The Institute for Supply Management® ("ISM") Report On Business® (both Manufacturing and Non-Manufacturing) ("ISM ROB") contains information, text, files, images, video, sounds, musical works, works of authorship, applications, and any other materials or content (collectively, "Content") of ISM ("ISM ROB Content"). ISM ROB Content is protected by copyright, trademark, trade secret, and other laws, and as between you and ISM, ISM owns and retains all rights in the ISM ROB Content. 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This prohibition applies regardless of whether the derivative works or materials are sold, bartered, or given away. You shall not either directly or through the use of any device, software, internet site, web-based service, or other means remove, alter, bypass, avoid, interfere with, or circumvent any copyright, trademark, or other proprietary notices marked on the Content or any digital rights management mechanism, device, or other content protection or access control measure associated with the Content including geo-filtering mechanisms. Without prior written authorization from ISM, you shall not build a business utilizing the Content, whether or not for profit. You shall not create, recreate, distribute, incorporate in other work, or advertise an index of any portion of the Content unless you receive prior written authorization from ISM. Requests for permission to reproduce or distribute ISM ROB Content can be made by contacting in writing at: ISM Research, Institute for Supply Management, 309 West Elliot Road, Suite 113, Tempe, Arizona 85284-1556, or by emailing [email protected]. Subject: Content Request. ISM shall not have any liability, duty, or obligation for or relating to the ISM ROB Content or other information contained herein, any errors, inaccuracies, omissions or delays in providing any ISM ROB Content, or for any actions taken in reliance thereon. In no event shall ISM be liable for any special, incidental, or consequential damages, arising out of the use of the ISM ROB. Report On Business®, PMI®, and NMI® are registered trademarks of Institute for Supply Management®. Institute for Supply Management® and ISM® are registered trademarks of Institute for Supply Management, Inc. About Institute for Supply Management ® Institute for Supply Management® (ISM®) serves supply management professionals in more than 90 countries. Its 50,000 members around the world manage about US$1 trillion in corporate and government supply chain procurement annually. Founded in 1915 as the first supply management institute in the world, ISM is committed to advancing the practice of supply management to drive value and competitive advantage for its members, contributing to a prosperous and sustainable world. ISM leads the profession through the ISM® Report On Business®, its highly regarded certification programs and the ISM® Advance™ Digital Platform. This report has been issued by the association since 1931, except for a four-year interruption during World War II. The full text version of the Manufacturing ISM® Report On Business® is posted on ISM®'s website at on the first business day* of every month after 10:00 a.m. ET. The next Manufacturing ISM® Report On Business® featuring December 2022 data will be released at 10:00 a.m. ET on Wednesday, January 4, 2023. *Unless the New York Stock Exchange is closed. SOURCE Institute for Supply Management

– DISSOLVE I & II studies of SEL-212 in Chronic Refractory Gout remain on track for joint topline data readout in Q1 2023 – – SEL-302, Selecta’s wholly owned gene therapy in combination with ImmTOR for the treatment of Methylmalonic Acidemia (MMA), remains on track to begin a Phase 1 trial in Q4 2022 – – As of September 30, 2022, Selecta had approximately $148.0 million in cash, cash equivalents, restricted cash and marketable securities, which is expected to provide runway into mid-2024 – – Candidate selection for an IL-2 and IgA protease expected by year-end 2022 – – Selecta to host conference call today at 8:30 AM ET – WATERTOWN, Mass., Nov. 03, 2022 (GLOBE NEWSWIRE) -- Selecta Biosciences, Inc. (NASDAQ: SELB), a biotechnology company pioneering precision immune tolerance with its clinically validated ImmTOR® platform to develop tolerogenic therapies for autoimmune diseases, unlock the potential of gene therapies and amplify the efficacy of biologic therapies, today reported financial results for the third quarter ended September 30, 2022 and provided a business update. “We are pleased with the steady progress seen across our clinical and pre-clinical pipelines. With expected financial runway into mid-2024 we believe we are well-positioned to execute on our key priorities and achieve multiple near-term value driving inflection points,” said Carsten Brunn, Ph.D., president and chief executive officer of Selecta. “Clinically, we remain on track to initiate the Phase 1 trial of SEL-302, our wholly owned gene therapy in combination with ImmTOR for the treatment of MMA in Q4 2022, and expect to report joint topline data from the Phase 3 DISSOLVE clinical program investigating SEL-212 in chronic refractory gout, in Q1 2023. Preclinically, with our external partners we continue to drive toward candidate selection for an IgA protease to treat IgA nephropathy, as well as progress IND-enabling studies and manufacturing scale-up for Xork, our proprietary IgG protease developed as a pre-treatment to enable AAV gene therapies. Finally, building on the recently presented data at ESGCT, we continue our work in identifying a proprietary IL-2 to combine with ImmTOR, which we anticipate announcing by year-end. We believe ImmTOR- IL™, based on the synergistic effects we have observed preclinically, has the potential to be a generational leap forward for our precision immune tolerance platform.” Recent Program Highlights and Anticipated Upcoming Milestones: Tolerogenic Therapies for Autoimmune Disease: ImmTOR-IL: Preclinically, Selecta has observed synergistic activity when ImmTOR is combined with engineered IL-2 molecules that are selective for Tregs (ImmTOR-IL™). Furthermore, when ImmTOR-IL was co-administered with an antigen of interest, the resulting data suggested that ImmTOR-IL may have profound synergistic effects in expanding antigen-specific Tregs when compared to ImmTOR alone, positioning ImmTOR-IL as a potential first-in-class antigen-specific therapy for the treatment of autoimmune disease. Selecta continues to work with its partners to develop a next generation IL-2 molecule to combine with ImmTOR and still anticipates selecting an IL-2 candidate by year-end 2022.Selecta continues internal work on identifying additional target indications in autoimmune disease. Selecta plans to adopt a staged development approach, starting first with diseases driven by a single pathogenic antigen, such as Primary Biliary Cholangitis (PBC), then accelerating development across related indications. Primary biliary cholangitis (PBC): Selecta intends to co-administer ImmTOR-IL with PDC-E2, the autoantigen implicated in PBC and continues IND-enabling work for this combination. Gene Therapies: SEL-302 for MMA: Selecta remains on track to initiate a Phase 1/2 clinical trial of SEL-302, an AAV gene therapy combined with ImmTOR for the treatment of MMA, in the fourth quarter of 2022. SEL-018 IgG Protease (Xork): In collaboration with Genovis, Selecta continues to advance Xork, a next-generation IgG protease, to help address disease in patients who are ineligible for gene therapies due to pre-existing anti-AAV antibodies. Selecta believes the novel combination of Xork and ImmTOR has the potential to address two of the key hurdles in gene therapy today: pre-existing immunity to AAVs and the inability to re-dose AAV gene therapies due to the immune response to AAV capsids. IND-enabling studies and manufacturing scale-up activities are ongoing. ImmTOR-IL: In October 2022, we presented preclinical data at the 29th Annual European Society of Gene and Cell Therapy (ESGCT) Conference further supporting the potential therapeutic utility of ImmTOR in enabling safe repeated vector dosing and mitigating unwanted immune responses. Additionally, we presented data in which we observed the potential of ImmTOR-IL in driving antigen-specific Treg expansion while synergistically inhibiting formation of anti-AAV antibodies at high vector doses. Biologic Therapies: SEL-212 for chronic refractory gout: Selecta continues to advance DISSOLVE, the Phase 3 development program of SEL-212, which has been licensed to Sobi. In Q3 2022, Selecta received a $10 million milestone payment from Sobi following the completion of enrollment of DISSOLVE II in June 2022.DISSOLVE I & II trials are on track for completion in Q1 2023 with joint topline readout expected in Q1 2023. ImmTOR with IgA protease for IgA nephropathy: Selecta continues to work with its partners to identify and develop a next generation IgA protease to combine with ImmTOR, and consistent with prior guidance anticipates selecting an enzyme candidate by year-end 2022. Further Corporate and Partnership Updates: In Q3 2022, and as previously disclosed, Selecta received a $2 million payment from Sarepta relating to the extension of its Research License and Option Agreement for ImmTOR in Duchenne Muscular Dystrophy (DMD) and certain Limb-Girdle Muscular Dystrophies (LGMD) for an additional nine months to Q1 2023, and an additional $4 million payment from Sarepta for achievement of certain preclinical milestones. Third Quarter 2022 Financial Results Cash Position: Selecta had $148.0 million in cash, cash equivalents, marketable securities, and restricted cash as of September 30, 2022, as compared to cash, cash equivalents, marketable securities, and restricted cash of $129.4 million as of December 31, 2021. Net cash used in operating activities was $19.8 million for the nine months ended September 30, 2022, as compared to $28.9 million of cash used in operating activities for the same period in 2021. Selecta believes its available cash, cash equivalents, restricted cash, and marketable securities will be sufficient to meet its operating requirements into mid-2024. Collaboration and License Revenue: Collaboration and license revenue for the third quarter of 2022 was $20.7 million, as compared to $24.4 million for the same period in 2021. Revenue was primarily driven by the shipment of clinical supply and the reimbursement of costs incurred for the Phase 3 DISSOLVE clinical program under the license agreement with Sobi. Research and Development Expenses: Research and development expenses for the third quarter of 2022 were $16.5 million, as compared to $21.0 million for the same period in 2021. The decrease in cost was primarily the result of a decrease in expenses incurred for the SEL-212 clinical program, preclinical programs, and the AskBio collaboration. General and Administrative Expenses: General and administrative expenses for the third quarter of 2022 were $5.8 million, as compared to $5.4 million for the same period in 2021. The increase in costs was primarily the result of expenses incurred for stock compensation and personnel expenses. Net loss: For the third quarter of 2022, Selecta reported net loss of $7.9 million, or basic net loss per share of $0.05, compared to net loss of $17.9 million, or basic net loss per share of $0.16, for the same period in 2021. Conference Call and Webcast ReminderSelecta management will host a conference call at 8:30 AM ET today to provide a business update and review the company’s third quarter 2022 financial results. Individuals may participate in the live call via telephone by dialing (844) 845-4170 (domestic) or +1 (412) 717-9621 (international) and may access a teleconference replay for one week by dialing (877) 344-7529 (domestic) or +1 (412) 317-0088 (international) and using confirmation code 10157874. Investors and the public can access the live and archived webcast of this call and a copy of the presentation via the Investors & Media section of the company’s website, www.selectabio.com. About Selecta Biosciences, Inc.Selecta Biosciences Inc. (NASDAQ: SELB) is a clinical stage biotechnology company leveraging its ImmTOR® platform to develop tolerogenic therapies that selectively mitigate unwanted immune responses. With a proven ability to induce tolerance to highly immunogenic proteins, ImmTOR has the potential to amplify the efficacy of biologic therapies, including redosing of life-saving gene therapies, as well as restore the body’s natural self-tolerance in autoimmune diseases. Selecta has several proprietary and partnered programs in its pipeline focused on enzyme therapies, gene therapies, and autoimmune diseases. Selecta Biosciences is headquartered in the Greater Boston area. For more information, please visit www.selectabio.com. Selecta Forward-Looking Statements Any statements in this press release about the future expectations, plans and prospects of Selecta Biosciences, Inc. (the “Company”), including without limitation, statements regarding the Company’s cash runway, the unique proprietary technology platform of the Company, and the unique proprietary platform of its partners, the potential of ImmTOR to enable re-dosing of AAV gene therapy and to mitigate immunogenicity, the potential of ImmTOR and the Company’s product pipeline to treat chronic refractory gout, MMA, IgAN, other autoimmune diseases, lysosomal storage disorders, or any other disease, the anticipated timing or the outcome of ongoing and planned clinical trials, studies and data readouts, the anticipated timing or the outcome of the FDA’s review of the Company’s regulatory filings, the Company’s and its partners’ ability to conduct its and their clinical trials and preclinical studies, the timing or making of any regulatory filings, the anticipated timing or outcome of selection of developmental product candidates, the potential treatment applications of product candidates utilizing the ImmTOR platform in areas such as gene therapy, gout and autoimmune disease, the ability of the Company and its partners where applicable to develop gene therapy products using ImmTOR, the novelty of treatment paradigms that the Company is able to develop, whether the observations made in non-human study subjects will translate to studies performed with human beings, the potential of any therapies developed by the Company to fulfill unmet medical needs, the Company’s plan to apply its ImmTOR technology platform to a range of biologics for rare and orphan genetic diseases, the potential of the Company’s technology to enable repeat administration in gene therapy product candidates and products, the ability to re-dose patients and the potential of ImmTOR to allow for re-dosing, the potential to safely re-dose AAV, the ability to restore transgene expression, the potential of the ImmTOR technology platform generally and the Company’s ability to grow its strategic partnerships and enrollment in the Company's clinical trials and other statements containing the words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “hypothesize,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including, but not limited to, the following: the uncertainties inherent in the initiation, completion and cost of clinical trials including proof of concept trials, including the uncertain outcomes, the availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary results from a particular clinical trial will be predictive of the final results of that trial and whether results of early clinical trials will be indicative of the results of later clinical trials, the ability to predict results of studies performed on human beings based on results of studies performed on non-human subjects, the unproven approach of the Company’s ImmTOR technology, potential delays in enrollment of patients, undesirable side effects of the Company’s product candidates, its reliance on third parties to manufacture its product candidates and to conduct its clinical trials, the Company’s inability to maintain its existing or future collaborations, licenses or contractual relationships, its inability to protect its proprietary technology and intellectual property, potential delays in regulatory approvals, the availability of funding sufficient for its foreseeable and unforeseeable operating expenses and capital expenditure requirements, the Company’s recurring losses from operations and negative cash flows, substantial fluctuation in the price of the Company’s common stock, risks related to geopolitical conflicts and pandemics and other important factors discussed in the “Risk Factors” section of the Company’s most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, and in other filings that the Company makes with the Securities and Exchange Commission. In addition, any forward-looking statements included in this press release represent the Company’s views only as of the date of its publication and should not be relied upon as representing its views as of any subsequent date. The Company specifically disclaims any intention to update any forward-looking statements included in this press release, except as required by law. For investors:Bruce MackleLifeSci Advisors, LLC+1-929-469-3859bmackle@lifesciadvisors.com For media: Brittany Leigh, Ph.D.LifeSci Communications, LLC+1-813-767-7801bleigh@lifescicomms.com Financial Tables Selecta Biosciences, Inc. and Subsidiaries Consolidated Balance Sheets (Amounts in thousands, except share data and par value) September 30, 2022 December 31, 2021 (Unaudited) Assets Current assets: Cash and cash equivalents$112,843 $114,057 Marketable securities 33,599 13,998 Accounts receivable 6,925 9,914 Prepaid expenses and other current assets 6,310 6,474 Total current assets 159,677 144,443 Non-current assets: Property and equipment, net 2,904 2,142 Right-of-use asset, net 12,056 9,829 Long-term restricted cash 1,600 1,379 Investments 2,000 2,000 Other assets 28 90 Total assets$178,265 $159,883 Liabilities and stockholders’ equity Current liabilities: Accounts payable$214 $224 Accrued expenses 12,263 10,533 Loan payable 5,879 5,961 Lease liability 1,552 1,049 Income taxes payable — 601 Deferred revenue 3,820 53,883 Total current liabilities 23,728 72,251 Non-current liabilities: Loan payable, net of current portion 20,215 19,673 Lease liability, net of current portion 10,506 8,598 Deferred revenue 5,436 11,417 Warrant liabilities 33,473 25,423 Total liabilities 93,358 137,362 Stockholders’ equity: Preferred stock, $0.0001 par value; 10,000,000 shares authorized; no shares issued and outstanding as of September 30, 2022 and December 31, 2021 — — Common stock, $0.0001 par value; 350,000,000 and 200,000,000 shares authorized as of September 30, 2022 and December 31, 2021, respectively; 153,028,822 and 123,622,965 shares issued and outstanding as of September 30, 2022 and December 31, 2021, respectively 15 12 Additional paid-in capital 490,252 457,391 Accumulated deficit (400,830) (430,316)Accumulated other comprehensive loss (4,530) (4,566)Total stockholders’ equity 84,907 22,521 Total liabilities and stockholders’ equity$178,265 $159,883 Selecta Biosciences, Inc. and Subsidiaries Consolidated Statements of Operations and Comprehensive Income (Loss) (Amounts in thousands, except share and per share data) Three Months EndedSeptember 30, Nine Months EndedSeptember 30, 2022 2021 2022 2021 (Unaudited) Collaboration and license revenue$20,710 $24,427 $93,982 $55,140 Operating expenses: Research and development 16,539 20,951 53,410 48,418 General and administrative 5,770 5,445 17,538 15,397 Total operating expenses 22,309 26,396 70,948 63,815 Operating income (loss) (1,599) (1,969) 23,034 (8,675)Investment income 710 11 932 35 Foreign currency transaction, net 15 2 (61) (5)Interest expense (802) (711) (2,224) (2,133)Change in fair value of warrant liabilities (6,539) 592 7,329 (11,335)Other income, net 1 9 155 15 Income (loss) before income taxes (8,214) (2,066) 29,165 (22,098)Income tax (expense) benefit 321 (15,828) 321 (15,828)Net income (loss)$(7,893) $(17,894) $29,486 $(37,926) Other comprehensive income (loss): Foreign currency translation adjustment (21) (1) 65 5 Unrealized loss on marketable securities (29) (1) (29) (1)Total comprehensive income (loss)$(7,943) $(17,896) $29,522 $(37,922) Net income (loss) per share: Basic$(0.05) $(0.16) $0.21 $(0.34)Diluted$(0.05) $(0.16) $0.15 $(0.34)Weighted average common shares outstanding: Basic 152,849,992 115,169,949 141,969,449 113,161,622 Diluted 152,849,992 115,169,949 143,792,060 113,161,622