Pyelonephritis

Phase 2a proof-of-concept study of SPR720 for the treatment of Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD) did not meet its primary endpoint, based on planned interim analysis of 16 patients Phase 3 PIVOT-PO trial of tebipenem HBr remains on track for enrollment completion in 2H 2025 Cash runway extended into mid-2026 following a reduction in workforce and restructuring of operations; Unaudited Q3 2024 ending cash balance of $76.3M CAMBRIDGE, Mass., Oct. 29, 2024 (GLOBE NEWSWIRE) -- Spero Therapeutics, Inc. (Nasdaq: SPRO), a multi-asset clinical-stage biopharmaceutical company, focused on identifying and developing novel treatments for rare diseases and multi-drug resistant (MDR) bacterial infections, today announced that a planned interim analysis of the Phase 2a proof-of-concept study of SPR720 for the treatment of NTM-PD demonstrated that the program did not meet its primary endpoint. While the data showed antimicrobial activity associated with SPR720, the interim analysis did not show sufficient separation from placebo and highlighted potential dose limiting safety issues in subjects dosed at 1,000 mg orally once daily, including three cases of reversible grade 3 hepatotoxicity. In evaluating the totality of both the efficacy and safety data, the Company has elected to suspend its current development program for SPR720 and will evaluate other potential paths forward as the remaining data are collected and analyzed. As a result of the suspension of the current SPR720 development program, Spero will undergo a restructuring and reduction in force of approximately 39%, which will extend cash runway and support operations into mid-2026, to further support the development of tebipenem HBr, SPR206, and potential strategic activities. “Spero launched its proof-of-concept clinical study for SPR720 as a monotherapy to evaluate its potential efficacy and safety in treating NTM-PD. While a planned interim analysis provided evidence of antimicrobial activity, the trial unfortunately did not meet the primary endpoint,” said Sath Shukla, Spero’s President and Chief Executive Officer. “We are therefore suspending development of the SPR720 program and making adjustments to our organization accordingly. I want to offer my sincere thanks to all our Spero SPR720 colleagues, along with our investigators and patients, for their dedication in seeking new treatment options for this devastating disease. We remain committed to bringing forward new treatment options for patients in need, as we continue to advance our tebipenem HBr and SPR206 programs.” Restructuring to Prioritize Programs and Capital Allocation Spero closed the third quarter ended September 30, 2024, with an unaudited cash estimate of $76.3 million. Following the reduction in force and restructuring, Spero estimates that its existing cash and cash equivalents, together with earned and non-contingent development milestone payments from GSK, as well as other non-dilutive funding commitments, will be sufficient to fund its operating expenses and capital expenditures into mid-2026. During this period, the Company remains focused on advancing tebipenem HBr in the ongoing global PIVOT-PO Phase 3 clinical trial and preparing for a Phase 2 clinical trial for SPR206 contingent on continued non-dilutive funding. SPR720SPR720 is an oral, chemically stable phosphate ester prodrug that is converted rapidly in vivo to SPR719, the active moiety. SPR719 targets the ATPase site of DNA gyrase B in mycobacteria, a mechanism that is distinct from that of other antibiotics in use for Non Tuberculous Mycobacterial-Pulmonary Disease (NTM-PD).Recent updates: Phase 2a trial – enrollment concluded in July 2024, with 25 non-refractory patients enrolled in the proof-of-concept trial evaluating SPR720 in NTM-PD. A planned interim analysis based on 16 patients indicated the trial did not meet its primary endpoint of differentiation from placebo in the rate of change in log10 colony forming units per milliliter (CFU/mL). In addition, analysis of the full 25 patient safety data highlighted potential dose limiting safety issues in patients dosed at 1,000mg orally once daily, including three cases of reversible grade 3 hepatotoxicity. The Company plans to complete data analysis of all enrolled patients (n=25) and determine the next steps for the SPR720 program over the next several months. For more information on the trial, see ClinicalTrials.gov identifier NCT05496374. Tebipenem HBrTebipenem HBr is an investigational oral carbapenem antibiotic being developed for the treatment of cUTI including acute pyelonephritis (AP) to help patients avoid hospitalizations or reduce duration of in-patient therapy. Spero granted GSK an exclusive license to commercialize tebipenem HBr in all territories, except certain Asian territories. Spero received $66 million upfront from GSK when the license agreement was signed in 2022, $30 million when the Company reached the Special Protocol Assessment milestone in Q3 2023, and was entitled to receive $95 million in development milestones upon enrollment of the first patient in the PIVOT-PO Phase 3 trial, $47.5 million of which have been received thus far. Spero is further eligible to receive up to $400 million in development, sales, and commercial milestones payments, as well as low single-digit to low double-digit tiered royalties on net product sales. Enrollment on track in PIVOT-PO, the global Phase 3 clinical trial of tebipenem HBr in patients with cUTI. This randomized, double-blinded trial compares oral tebipenem HBr with intravenous imipenem cilastatin, in hospitalized adult patients with cUTI/AP. The primary endpoint is overall response (a combination of clinical cure and favorable microbiological response) at the Test-of-Cure (TOC) visit. Target enrollment for the trial is approximately 2,648 patients, with enrollment completion expected in the second half of 2025. For more information on PIVOT-PO, refer to ClinicalTrials.gov ID NCT06059846. SPR206SPR206 is an investigational, intravenously administered next-generation polymyxin that has shown antibiotic activity against MDR Gram-negative pathogens, including carbapenem-resistant Enterobacterales, Acinetobacter baumannii and Pseudomonas aeruginosa in preclinical studies. The U.S. Food and Drug Administration (FDA) cleared the Company's IND for a Phase 2 trial in participants with hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP). The Company maintains its guidance to initiate the trial, contingent on availability of non-dilutive funding. About Spero TherapeuticsSpero Therapeutics, headquartered in Cambridge, Massachusetts, is a multi-asset clinical-stage biopharmaceutical company focused on identifying and developing novel treatments for rare diseases and MDR bacterial infections with high unmet need. For more information, visit www.sperotherapeutics.com Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, the timing, progress and results of the Company’s preclinical studies, clinical trials and research and development programs; management’s assessment of the results of such preclinical studies and clinical trials; and the expected cost-savings from the Company’s reduction in workforce and restructuring of its operations, the Company’s anticipated expenses and its anticipated cash runway . In some cases, forward-looking statements may be identified by terms such as "may," "will," "should," "expect," "plan," "aim," "anticipate," "could," "intent," "target," "project," "contemplate," "believe," "estimate," "predict," "potential" or "continue," the negative of these terms or other similar expressions. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of important risks, uncertainties and other factors that may cause actual results to differ materially from those indicated by such forward looking statements, including whether tebipenem HBr, SPR720 and SPR206 will advance through the clinical trial process on a timely basis, or at all, taking into account the effects of possible regulatory delays, slower than anticipated patient enrollment, manufacturing challenges, clinical trial design and clinical outcomes; whether the results of such trials will warrant submission for approval from the FDA or equivalent foreign regulatory agencies; whether the FDA will ultimately approve tebipenem HBr and, if so, the timing of any such approval; whether the FDA will require any additional clinical data or place labeling restrictions on the use of tebipenem HBr that would delay approval and/or reduce the commercial prospects of tebipenem HBr; whether a successful commercial launch can be achieved and market acceptance of tebipenem HBr can be established; whether results obtained in preclinical studies and clinical trials will be indicative of results obtained in future clinical trials; Spero's reliance on third parties to manufacture, develop, and commercialize its product candidates, if approved; Spero's need for additional funding; the ability to commercialize Spero's product candidates, if approved; Spero's ability to retain key personnel; Spero's leadership transitions; whether Spero's cash resources will be sufficient to fund its continuing operations for the periods and/or trials anticipated; and other factors discussed in the "Risk Factors" set forth in filings that Spero periodically makes with the SEC. The forward-looking statements included in this press release represent Spero's views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Spero explicitly disclaims any obligation to update any forward-looking statements. Investor Relations Contact:Shai Biran, PhDSpero Therapeutics IR@Sperotherapeutics.com Media Inquiries: media@sperotherapeutics.com

Following strong protection (84% relative risk reduction versus placebo) demonstrated through month 6 with pemivibart, CANOPY clinical trial participants were followed for an additional six-month period (months 7-12), with no additional doses, to assess safety and efficacy as drug concentrations declined over timeIn the six-month off-drug follow-up period (months 7-12), substantially reduced concentrations of PEMGARDA reduced the risk of symptomatic COVID-19 by 64% compared to placebo in an immunocompetent adult population, for total twelve-month risk reduction of 76% following two initial pemivibart doses (nominal p <0.0001)Months 7-12 follow-up period included the U.S. summer KP.3 and KP.3.1.1 dominant wave, per CDC surveillanceNo new safety observations occurred months 7-12Across all 12 months of the CANOPY clinical trial, Cohort B placebo arm participants experienced an 18% rate of PCR-confirmed symptomatic COVID-19, excluding reinfections, indicative of continued, widespread, uncontrolled virus transmission in the U.S. WALTHAM, Mass., Oct. 29, 2024 (GLOBE NEWSWIRE) -- Invivyd, Inc. (Nasdaq: IVVD), a biopharmaceutical company devoted to delivering protection from serious viral infectious diseases, today announced positive 12-month exploratory clinical efficacy data from the company’s ongoing CANOPY Phase 3 clinical trial of pemivibart, a half-life extended investigational monoclonal antibody (mAb), for the pre-exposure prophylaxis (PrEP) of COVID-19. The exploratory clinical efficacy data from follow-up months 7-12 in CANOPY Cohort B, a placebo-controlled cohort of immunocompetent individuals at risk for symptomatic COVID-19 disease due to regular unmasked face-to-face indoor interactions, showed a relative risk reduction (RRR) of 64% in the pemivibart arm compared to placebo in the likelihood of trial participants contracting confirmed symptomatic COVID-19. Continued protection over this follow-up period, absent continued dosing, was a prespecified exploratory endpoint and, added to initial 180-day clinical efficacy observations, generated an overall 12-month protection rate of 76% following two doses of pemivibart (administered on Days 1 and 90), nominally significant at <0.0001. Clinical efficacy data are displayed in the table below. Placebo Arm Pemivibart Arm Nominal SubjectsCOVID-19 CasesAttack Rate SubjectsCOVID-19 CasesAttack Rate RRR*** p valueOn-drug Period 0-6 months*1601911.9% 31761.9% 84% <0.0001 Long-term Follow-up Period Following Cessation of Dosing 0-9 months1602012.5% 31782.5% 80% <0.00010-12 months1602918.1% 317144.4% 76% <0.00017-12 months**133107.5% 28982.8% 64% 0.0285 * Period includes US JN.1 wave ** Period includes US KP.3 and KP.3.1.1 wave *** Relative risk reduction excludes deaths unrelated to COVID-19 Pemivibart has an estimated in vivo half-life of approximately 45 days, and pemivibart IC50 values against circulating viruses are tested routinely, allowing for the calculation of the average serum virus neutralizing antibody (sVNA) titer over time, the measure of how much antiviral activity pemivibart confers to treated participants. Previously published literature1 indicates likely robust protection from symptomatic COVID-19 at sVNA titer levels well below the levels delivered by the authorized PEMGARDA (pemivibart) dosing regimen. In this updated CANOPY exploratory analysis, the 64% RRR (excluding deaths unrelated to COVID-19) that residual circulating pemivibart delivered versus placebo in months 7 through 12 occurred at calculated average titers of only approximately 7% of the average titers during the active dosing period. This was attributable to the expected decline in pemivibart serum concentrations following cessation of dosing, along with modest change to assessed pemivibart IC50 in the transition from the JN.1 dominant virus to the KP lineage dominant circulating viruses. “Today’s data underline our high confidence in the clinical benefit that mAbs like pemivibart can confer even at very low serum concentrations and associated antiviral titers,” commented Robert Allen, Ph.D., Chief Scientific Officer of Invivyd. “Engineered mAbs are designed to confer a step change in protection compared to the protection possible from native immune response to infection and vaccination boosts2. We believe that the clinical risk reduction generated at such low titers in this CANOPY clinical trial follow-up, which builds on now longstanding published data, implies that the modest changes (less than ~10 fold change) in pemivibart IC50 observed against emerging variants are of questionable significance.” “Our company’s goal is to provide high quality options for protection from SARS-CoV-2. Today’s exploratory clinical efficacy data update from our Phase 3 trial is critical, as it adds contemporary context to longstanding data showing strong protection from COVID-19 disease at relatively low sVNA titers with mAbs,” commented Marc Elia, Chairman of the Invivyd Board of Directors. “These consistent observations now span years and countless virus lineages and mutations, and, in toto, suggest that Invivyd, pending alignment with regulators, can develop and commercialize low-dose, high potency, long-acting mAbs that can have the same route of administration and system-friendliness as COVID-19 vaccine boosts, but with the goal of higher, more consistent, and longer-acting protection. Our current pipeline molecule, VYD2311, is currently in Phase 1 testing including an intramuscular (IM) administration in anticipation of executing against this exact goal.” The safety profile of pemivibart over the 12-month study period was reassuring with no new trends or safety signals observed for treatment-emergent adverse events (TEAEs) or infusion-related reactions or hypersensitivity reactions since the disclosure of the 6-month CANOPY data. Over the 12 months, in Cohort A, an open-label single-arm cohort, the most common TEAEs (>5%) included upper respiratory tract infection (URTI) (10.1%), viral infection (8.8%), urinary tract infection (UTI) (5.6%), and influenza-like illness (5.2%). As previously disclosed, anaphylaxis was observed in 4 participants (0.6%) in Cohort A – 2 participants during the first infusion and 2 participants during the second infusion; two reactions were life-threatening, and all led to permanent discontinuation of pemivibart. Infusion-related reactions and hypersensitivity reactions within 24 hours of dosing pemivibart were observed in 8.2% and 3.9% of participants in Cohort A after the initial dose and redose, respectively, and were generally mild to moderate in severity. Over the 12 months, in Cohort B, the most common TEAEs in the pemivibart arm included viral infection (8.5%), URTI (8.5%), and influenza-like illness (5.7%), with higher percentages in the placebo arm. No participants developed anaphylaxis. Infusion-related reactions and hypersensitivity reactions within 24 hours of dosing pemivibart were observed in 1.3% and 2.5% of participants in Cohort B after initial dose and redose, respectively, and were all mild or moderate in severity. Serious Adverse Events (SAEs) occurring in >1 Cohort A participant included pneumonia (n=3), anaphylactic reaction (n=2), hypotension (n=2), pyelonephritis (n=2), syncope (n=2), and UTI (n=2). No SAEs occurred in >1 participant in either treatment arm in Cohort B. These data support that the safety profile for pemivibart remains consistent with the PEMGARDA Fact Sheet for Healthcare Providers and the known safety profile of other SARS-CoV-2-directed mAbs. CANOPY Cohort B exploratory clinical efficacy results from months 7-12 provide data from reduced concentration of pemivibart and reduced sVNA titers in a contemporary immunocompetent population that had acquired prior immune exposure from either vaccination or natural infection and overlapped with the height of the Summer 2024 KP.3 and KP3.1.1 wave that saw a surge in COVID-19 cases nationwide in the U.S. By contrast, ancestral clinical trials of prior COVID-19 PrEP candidate mAbs were performed in populations naïve to vaccination or infection. The months’ 7-12 CANOPY Cohort B clinical efficacy exploratory data announced today complement the 180-day clinical efficacy exploratory data demonstrating potential signals of clinical protection from symptomatic COVID-19 shared previously. The company expects the full data set to be provided in an upcoming scientific publication. About InvivydInvivyd, Inc. (Nasdaq: IVVD) is a biopharmaceutical company devoted to delivering protection from serious viral infectious diseases, beginning with SARS-CoV-2. The company’s proprietary INVYMAB™ platform approach combines state-of-the-art viral surveillance and predictive modeling with advanced antibody engineering. INVYMAB is designed to facilitate the rapid, serial generation of new monoclonal antibodies (mAbs) to address evolving viral threats. In March 2024, Invivyd received emergency use authorization (EUA) from the U.S. FDA for its first mAb in a planned series of innovative antibody candidates. Visit https://invivyd.com/ to learn more. About PEMGARDA PEMGARDA™ (pemivibart) is a half-life extended investigational monoclonal antibody (mAb). PEMGARDA was engineered from adintrevimab, Invivyd’s investigational mAb that has a robust safety data package and provided evidence of clinical efficacy in a global Phase 2/3 clinical trial for the prevention and treatment of COVID-19. PEMGARDA has demonstrated in vitro neutralizing activity against major SARS-CoV-2 variants, including JN.1. PEMGARDA targets the SARS-CoV-2 spike protein receptor binding domain (RBD), thereby inhibiting virus attachment to the human ACE2 receptor on host cells. PEMGARDA (pemivibart) injection (4500 mg), for intravenous use is an investigational mAb that has not been approved, but has been authorized for emergency use by the U.S. FDA under an EUA for the pre-exposure prophylaxis (prevention) of COVID-19 in adults and adolescents (12 years of age and older weighing at least 40 kg) who have moderate-to-severe immune compromise due to certain medical conditions or receipt of certain immunosuppressive medications or treatments and are unlikely to mount an adequate immune response to COVID-19 vaccination. Recipients should not be currently infected with or have had a known recent exposure to an individual infected with SARS-CoV-2. PEMGARDA is not authorized for use for treatment of COVID-19 or post-exposure prophylaxis of COVID-19. Pre-exposure prophylaxis with PEMGARDA is not a substitute for vaccination in individuals for whom COVID-19 vaccination is recommended.  Individuals for whom COVID-19 vaccination is recommended, including individuals with moderate-to-severe immune compromise who may derive benefit from COVID-19 vaccinations, should receive COVID-19 vaccination.  In individuals who have recently received a COVID-19 vaccine, PEMGARDA should be administered at least 2 weeks after vaccination. Anaphylaxis has been observed with PEMGARDA and the PEMGARDA Fact Sheet for Healthcare Providers includes a boxed warning for anaphylaxis. The most common adverse events (all grades, incidence ≥2%) observed in participants who have moderate-to-severe immune compromise treated with PEMGARDA included systemic and local infusion-related or hypersensitivity reactions, upper respiratory tract infection, viral infection, influenza-like illness, fatigue, headache, and nausea. For additional information, please see the PEMGARDA full product Fact Sheet for Healthcare Providers, including important safety information and boxed warning. To support the EUA for PEMGARDA, an immunobridging approach was used to determine if PEMGARDA may be effective for pre-exposure prophylaxis of COVID-19. Immunobridging is based on the serum virus neutralizing titer-efficacy relationships identified with other neutralizing human mAbs against SARS-CoV-2. This includes adintrevimab, the parent mAb of pemivibart, and other mAbs that were previously authorized for EUA. There are limitations of the data supporting the benefits of PEMGARDA. Evidence of clinical efficacy for other neutralizing human mAbs against SARS-CoV-2 was based on different populations and SARS-CoV-2 variants that are no longer circulating. Further, the variability associated with cell-based EC50 value determinations, along with limitations related to pharmacokinetic data and efficacy estimates for the mAbs in prior clinical trials, impact the ability to precisely estimate protective titer ranges. Additionally, certain SARS-CoV-2 viral variants may emerge that have substantially reduced susceptibility to PEMGARDA, and PEMGARDA may not be effective at preventing COVID-19 caused by these SARS-CoV-2 viral variants. The emergency use of PEMGARDA is only authorized for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biological products during the COVID-19 pandemic under Section 564(b)(1) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization revoked sooner. PEMGARDA is authorized for use only when the combined national frequency of variants with substantially reduced susceptibility to PEMGARDA is less than or equal to 90%, based on available information including variant susceptibility to PEMGARDA and national variant frequencies. About CANOPY The ongoing CANOPY Phase 3 clinical trial is designed to evaluate the safety and tolerability of pemivibart and to assess immunobridging from pemivibart to certain historical data from the company’s previous Phase 2/3 clinical trial of adintrevimab (ADG20) for the prevention of symptomatic COVID-19 (EVADE). Additionally, there are pre-specified exploratory endpoints through three, six and twelve months to evaluate clinical efficacy of pemivibart compared to placebo in the prevention of RT-PCR-confirmed symptomatic COVID-19. The latest analysis from the Phase 3 CANOPY clinical trial includes 365-day data. The CANOPY clinical trial enrolled participants in two cohorts: Cohort A is a single-arm, open-label trial in adults who have moderate-to-severe immune compromise including complex underlying medical conditions. Cohort B is a randomized, placebo-controlled cohort that enrolled adults without moderate-to-severe immune compromise who are at risk of acquiring COVID-19 due to regular unmasked face-to-face interactions in indoor settings. Cautionary Note Regarding Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “anticipates,” “believes,” “could,” “expects,” “estimates,” “intends,” “potential,” “projects,” and “future” or similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements include statements concerning, among other things, the company’s ongoing research and clinical development activities, as well as future potential research and clinical development efforts; the potential clinical benefit that mAbs like PEMGARDA (pemivibart) can confer, even at very low serum concentrations and associated antiviral titers; the possibility for Invivyd to develop and commercialize low-dose, high potency, long-acting mAbs with the same route of administration and system-friendliness as COVID-19 vaccine boosts, but higher, more consistent, and longer-acting protection; the company’s expectation to provide a full data set from the CANOPY clinical trial in an upcoming scientific publication; the potential of PEMGARDA as a mAb for pre-exposure prophylaxis (prevention) of COVID-19 in certain adults and adolescents who have moderate-to-severe immune compromise; the company’s devotion to delivering protection from serious viral infectious diseases, beginning with SARS-CoV-2; the design of the company’s INVYMAB platform approach to facilitate the rapid, serial generation of new mAbs to address evolving viral threats; the company’s plans for a series of innovative antibody candidates and its goals for pipeline molecule VYD2311; and other statements that are not historical fact. The company may not actually achieve the plans, intentions or expectations disclosed in the company’s forward-looking statements and you should not place undue reliance on the company’s forward-looking statements. These forward-looking statements involve risks and uncertainties that could cause the company’s actual results to differ materially from the results described in or implied by the forward-looking statements, including, without limitation: the timing, progress and results of the company’s discovery, preclinical and clinical development activities; the risk that results of nonclinical studies or clinical trials may not be predictive of future results, and interim data are subject to further analysis; unexpected safety or efficacy data observed during preclinical studies or clinical trials; the predictability of clinical success of the company’s product candidates based on neutralizing activity in nonclinical studies; potential variability in neutralizing activity of product candidates tested in different assays, such as pseudovirus assays and authentic assays; the company’s reliance on third parties with respect to virus assay creation and product candidate testing and with respect to its clinical trials; variability of results in models used to predict activity against SARS-CoV-2 variants; whether pemivibart, VYD2311, or any other product candidate is able to demonstrate and sustain neutralizing activity against major SARS-CoV-2 variants, particularly in the face of viral evolution; how long the EUA granted by the FDA for PEMGARDA will remain in effect and whether the EUA is revised or revoked by the FDA; the company’s ability to build and maintain sales, marketing and distribution capabilities to successfully commercialize PEMGARDA; uncertainties related to the regulatory authorization or approval process, and available development and regulatory pathways for authorization or approval of the company’s product candidates; the ability to maintain a continued acceptable safety, tolerability and efficacy profile of any product candidate following regulatory authorization or approval; changes in the regulatory environment; changes in expected or existing competition; the complexities of manufacturing mAb therapies; the company’s ability to leverage its INVYMAB platform approach to facilitate the rapid, serial generation of new mAbs to address evolving viral threats; any legal proceedings or investigations relating to the company; the company’s ability to continue as a going concern; and whether the company has adequate funding to meet future operating expenses and capital expenditure requirements. Other factors that may cause the company’s actual results to differ materially from those expressed or implied in the forward-looking statements in this press release are described under the heading “Risk Factors” in the company’s Annual Report on Form 10-K for the year ended December 31, 2023 and the company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, each filed with the Securities and Exchange Commission (SEC), and in the company’s other filings with the SEC, and in its future reports to be filed with the SEC and available at www.sec.gov. Forward-looking statements contained in this press release are made as of this date, and Invivyd undertakes no duty to update such information whether as a result of new information, future events or otherwise, except as required under applicable law. This press release contains hyperlinks to information that is not deemed to be incorporated by reference in this press release. Contacts:Media Relations(781) 208-1747media@invivyd.com Investor Relations(781) 208-1747investors@invivyd.com 1Schmidt, et al. Antibody-Mediated Protection Against Symptomatic COVID-19 Can Be Achieved at Low Serum Neutralizing Titers. Sci. Transl. Med. 15, eadg2783 (2023); Stadler, et al. Monoclonal Antibody Levels and Protection From COVID-19, Nat. Commun., 14:4545 (2023) 2 https://www-cdc-gov.libproxy1.nus.edu.sg/acip/downloads/slides-2024-06-26-28/03-COVID-Link-Gelles-508.pdf

-Lexicon to receive an upfront payment of $25 million and the potential for contingent regulatory and commercial milestone paymentsTHE WOODLANDS, Texas, Oct. 16, 2024 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced that Viatris Inc. (Nasdaq: VTRS) has obtained an exclusive license from Lexicon to commercialize sotagliflozin outside of the United States and Europe in all indications. Lexicon retains sole commercialization rights for sotagliflozin in all indications in the United States and Europe. Sotagliflozin was approved by the U.S. Food and Drug Administration in May 2023 to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors. “We are pleased to be working with Viatris, a company with strong cardiometabolic expertise, global commercial capabilities and a successful track record of launching medicines in new territories. We are confident that this agreement will expand the reach of sotagliflozin to more patients in need,” said Dr. Mike Exton, Ph.D., chief executive officer and director of Lexicon. “Partnering with high quality companies to support commercialization of our medicines globally is a critical pillar of our Lead to Succeed strategy at Lexicon. We plan to continue to evaluate strategic partnerships for additional assets, territories and indications to augment Lexicon’s development and commercial capabilities, advance our pipeline and expand access of our medicines to more patients around the world.” Viatris chief commercial officer Corinne Le Goff said: “This licensing agreement with Lexicon adds another asset to our expanding innovative portfolio in cardiovascular diseases which gives us the opportunity to further drive accelerated and durable revenue growth in the future. We believe we will be able to leverage our strong foundation in cardiovascular diseases and our unique infrastructure to execute on the potential of sotagliflozin. We look forward to working with Lexicon to make a real difference and expand access for patients.” Under the terms of the agreement, Viatris has acquired rights to sotagliflozin in all global markets outside of the U.S. and Europe in exchange for an upfront payment to Lexicon of $25 million, and the potential for contingent regulatory and sales milestone payments and tiered royalties ranging from low-double-digit to upper-teens on annual net sales. Viatris will be responsible for all regulatory and commercialization activities for sotagliflozin in the licensed territories. Lexicon will be responsible for providing clinical and commercial supply of sotagliflozin to Viatris at an agreed upon transfer price. About Lexicon Pharmaceuticals Lexicon is a biopharmaceutical company with a mission of pioneering medicines that transform patients’ lives. Through its Genome5000™ program, Lexicon scientists studied the role and function of nearly 5,000 genes and identified more than 100 protein targets with significant therapeutic potential in a range of diseases. Through the precise targeting of these proteins, Lexicon is pioneering the discovery and development of innovative medicines to safely and effectively treat disease. Lexicon is commercially launching one of these medicines, INPEFA® (sotagliflozin) in the United States, and has a pipeline of other promising drug candidates in discovery and clinical and preclinical development in neuropathic pain, diabetes and metabolism and other indications. For additional information, please visit www.lexpharma.com. About ViatrisViatris Inc. (Nasdaq: VTRS) is a global healthcare company uniquely positioned to bridge the traditional divide between generics and brands, combining the best of both to more holistically address healthcare needs globally. With a mission to empower people worldwide to live healthier at every stage of life, Viatris provides access at scale, currently supplying high-quality medicines to approximately 1 billion patients around the world annually and touching all of life’s moments, from birth to the end of life, acute conditions to chronic diseases. With its exceptionally extensive and diverse portfolio of medicines, a one-of-a-kind global supply chain designed to reach more people when and where they need them, and the scientific expertise to address some of the world’s most enduring health challenges, access takes on deep meaning at Viatris. Viatris is headquartered in the U.S., with global centers in Pittsburgh, Shanghai and Hyderabad, India. Learn more at viatris.com and investor.viatris.com, and connect with Viatris on LinkedIn, Instagram, YouTube and X (formerly Twitter). About SotagliflozinDiscovered using Lexicon’s unique approach to gene science, sotagliflozin is an oral inhibitor of two proteins responsible for glucose regulation known as sodium-glucose cotransporter types 2 and 1 (SGLT2 and SGLT1). SGLT2 is responsible for glucose and sodium reabsorption by the kidney and SGLT1 is responsible for glucose and sodium absorption in the gastrointestinal tract. Sotagliflozin has been studied in multiple patient populations encompassing heart failure, diabetes, and chronic kidney disease in clinical studies involving approximately 20,000 patients. INDICATION INPEFA is indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with:  heart failure or  type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors  IMPORTANT SAFETY INFORMATION  Dosing: Assess renal function and volume status and, if necessary, correct volume depletion prior to initiation of INPEFA.  INPEFA dosing for patients with decompensated heart failure may begin when patients are hemodynamically stable, including when hospitalized or immediately upon discharge.  Contraindications: INPEFA is contraindicated in patients with hypersensitivity to INPEFA or any of its components.  Ketoacidosis: INPEFA increases the risk of ketoacidosis in patients with type 1 diabetes mellitus (T1DM).  Type 2 diabetes Mellitus (T2DM) and pancreatic disorders are also risk factors.  The risk of ketoacidosis may be greater with higher doses.  There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes using sodium glucose transporter 2 (SGLT2) inhibitors.  Before initiating INPEFA, assess risk factors for ketoacidosis. Consider ketone monitoring in patients with T1DM and consider ketone monitoring in others at risk for ketoacidosis and educate patients on the signs/symptoms of ketoacidosis.  Patients receiving INPEFA may require monitoring and temporary discontinuation of therapy in clinical situations known to predispose to ketoacidosis.  INPEFA is not indicated for glycemic control.  Assess patients who present with signs and symptoms of metabolic acidosis or ketoacidosis, regardless of blood glucose level.  If suspected, discontinue INPEFA, evaluate, and treat promptly.  Monitor patients for resolution of ketoacidosis before restarting INPEFA.  Volume Depletion: INPEFA can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine.  There have been post-marketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors.  Patients with impaired renal function (eGFR < 60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension.  Before initiating INPEFA in patients with one or more of these characteristics, assess volume status and renal function, and monitor for signs and symptoms of hypotension during therapy.  Urosepsis and Pyelonephritis: Treatment with SGLT2 inhibitors, including INPEFA, increases the risk for urinary tract infections.  Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been reported. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly.  Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Insulin and insulin secretagogues are known to cause hypoglycemia.  INPEFA may increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue.  Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used with INPEFA. Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Reports of Fournier’s Gangrene, a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have been identified in post-marketing surveillance in patients with diabetes mellitus receiving SGLT2 inhibitors.  Assess patients who present with pain, tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement.  Discontinue INPEFA, closely monitor patient signs and symptoms, and provide appropriate alternative therapy for heart failure.  Genital Mycotic Infections: INPEFA increases the risk of genital mycotic infections.  Monitor and treat as appropriate.  Urinary Glucose Test and 1,5-anhydroglucitol (1,5-AG) Assay: these are not reliable for patients taking SGLT2 inhibitors.  Use alternative testing methods to monitor glucose levels.   Common Adverse Reactions: the most commonly reported adverse reactions (incidence ≥ 5%) were urinary tract infection, volume depletion, diarrhea, and hypoglycemia.  Drug Interactions:  Digoxin: Monitor patients appropriately as there is an increase in the exposure of digoxin when coadministered with INPEFA 400 mg. Uridine 5'-diphospho-glucuronosyltransferase (UGT) Inducer: The coadministration of rifampicin, an inducer of UGTs, with sotagliflozin resulted in a decrease in the exposure of sotagliflozin.   Lithium: Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations.  Monitor serum lithium concentration more frequently during INPEFA initiation and with dosage changes.  Use in Specific Populations:  Pregnancy and Lactation: INPEFA is not recommended during the second and third trimesters of pregnancy, nor while breastfeeding.  Geriatric Use: No INPEFA dosage change is recommended based on age.  No overall differences in efficacy were detected between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.  Elderly patients may be at increased risk for volume depletion adverse reactions, including hypotension.Renal Impairment: INPEFA was evaluated in patients with chronic kidney disease (eGFR 25 to 60 mL/min/1.73 m2) and in patients with heart failure with eGFR < 60 mL/min/1.73 m2.  The safety profile of INPEFA across eGFR subgroups in these studies was consistent with the known safety profile.  There was an increase in volume-related adverse events (e.g., hypotension, dizziness) in patients with eGFR < 30 mL/min/1.73m2 relative to the overall safety population.  Efficacy and safety studies with INPEFA did not enroll patients with an eGFR less than 25 mL/min/1.73 m2 or on dialysis.  After starting therapy in the studies, patients were discontinued if eGFR fell below 15 mL/min/1.73 m2 or were initiated on chronic dialysis.Hepatic Impairment: INPEFA is not recommended in patients with moderate or severe hepatic impairment. Click here for full Prescribing Information. https://www.lexpharma.com/inpefa-US-PI.pdf Safe Harbor Statement This press release contains “forward-looking statements,” including statements relating to Lexicon’s financial position and long-term outlook on its business, growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including Lexicon’s ability to meet its capital requirements, successfully commercialize INPEFA in heart failure on the timeline and/or at the prices currently contemplated or at all, conduct preclinical and clinical development and obtain necessary regulatory approvals of sotagliflozin (in other indications), LX9211, LX9851 and its other drug candidates on its anticipated timelines, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug candidates. Any of these risks, uncertainties and other factors may cause Lexicon’s actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2023 and other subsequent disclosure documents filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise. For Media and Investor Inquiries: Lisa DeFrancescoLexicon Pharmaceuticals, Inc.lexinvest@lexpharma.com