A Phase 1/2 Study of MPH966, an Oral Neutrophil Elastase Inhibitor, for Prevention of Graft-versus-host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

The purpose of this study is evaluate the safety and tolerability of MPH966, a neutrophil elastase inhibitor, and its ability to prevent graft-versus-host disease after hematopoietic stem cell transplant.

Start Date01 Sep 2021

Sponsor / Collaborator

Duke University

[+2]

NCT04539795

/ CompletedPhase 1/2IIT

A Phase Ib/II, Single Center, Placebo-Controlled, Randomized, Blinded Study in Adult Patients (> 18 Years) With COVID-19 Respiratory Disease, to Evaluate, Safety, Tolerability and Mechanistic Effect of Alvelestat on Top of Standard of Care (COSTA)

The purpose of this study is to determine the safety, tolerability and pharmacokinetics (PK), and explore the mechanistic and clinical effect of alvelestat (an oral neutrophil elastase inhibitor) orally twice per day for 10 days added to standard of care in adult patients (≥18 years) with COVID-19 respiratory disease.

Start Date25 Jan 2021

Sponsor / Collaborator

The University of Alabama at Birmingham

[+1]

NCT03679598

/ CompletedPhase 2IIT

A First in Class Disease Modifying Therapy to Treat Alpha-1 Antitrypsin Deficiency a Genetically Linked Orphan Disease

This is a Phase 2, multicenter, double-blind, randomized (1:1), placebo-controlled, 12-week, proof-of-concept study to evaluate the safety and tolerability as well as the mechanistic effect of oral administration of alvelestat (MPH966) in subjects with confirmed AATD defined as Pi*ZZ, Pi*SZ, Pi*null, or another rare phenotype/genotype known to be associated with either low (serum AAT level <11 μM or <57.2 mg/dL) or functionally impaired AAT including "F" or "I" mutations.

Start Date08 Apr 2019

Sponsor / Collaborator

The University of Alabama at Birmingham

[+3]

100 Clinical Results associated with Alvelestat

100 Translational Medicine associated with Alvelestat

100 Patents (Medical) associated with Alvelestat

Literatures (Medical) associated with Alvelestat

01 Feb 2025·JOURNAL OF MOLECULAR STRUCTURE

Multi-step synthesis, kinetics and in silico explorations of indole-Phenyl-1,2,4-triazole Bi-heterocyclic hybrids unified with 3-substituted benzamides as elastase inhibitors

Author: Nazir, Majid ; Abbasi, Muhammad Athar ; Raza, Hussain ; Aziz-ur-Rehman ; Siddiqui, Sabahat Zahra ; Shakila ; Chaudhry, Aijaz Rasool ; Shahid, Muhammad ; Shah, Syed Adnan Ali ; Kim, Song Ja ; Muhammad, Shabbir

In the present research work, a library of unique indole-phenyltriazole hybrids comprising 3-substituted-benzamide moiety was synthesized through convergent multi-step strategy.The structural confirmation of all synthesized mols. was corroborated by IR, ¹H NMR, ¹³C MMR, EI-MS and CHN anal. data.The results of in vitro inhibitory potential of novel benzamides against elastase enzyme revealed that all mols. were potent inhibitors and 10d was most active compound among them having IC₅₀ value of (0.197 ± 0.027 μM), relative to the standard (13.421 ± 0.016 μM).The Kinetics mechanism analyzed by Lineweaver-Burk plots which exposed that 10d inhibited this enzyme competitively by forming an enzyme-inhibitor complex.The inhibition constant Ki determined from Dixon plot for compound 10d was 0.85 μM.Moreover, cytotoxicity of these compounds was also profiled by hemolytic activity and it was observed that almost all these benzamides compounds displayed low cytotoxicity.These mols. also exhibited mild cytotoxicity toward red blood cell membrane.In addition, the in silico computational explorations fully supported the in vitro enzyme inhibitory results.The binding energy ranges from -7.1 to -9.1 kcal/mol, which showed that compound possessed good interaction tendencies to the pancreatic elastase target protein.So, it was anticipated from the exptl. results and computational investigations of the current research that these derivatives might lead to further research gateways for obtaining better and safe nontoxic medicinal scaffolds for dealing with the elastase related ailments such as lungs diseases, pruritic skin disease and liver infection.

02 Aug 2024·SAR AND QSAR IN ENVIRONMENTAL RESEARCH

Robustaflavone as a novel scaffold for inhibitors of native and auto-proteolysed human neutrophil elastase

Article

Author: Singh, V. ; Bhatnagar, S. ; Kumar, Y.

Human neutrophil elastase (HNE) plays a key role in initiating inflammation in the cardiopulmonary and systemic contexts. Pathological auto-proteolysed two-chain (tc) HNE exhibits reduced binding affinity with inhibitors. Using AutoDock Vina v1.2.0, 66 flavonoid inhibitors, sivelestat and alvelestat were docked with single-chain (sc) HNE and tcHNE. Schrodinger PHASE v13.4.132 was used to generate a 3D-QSAR model. Molecular dynamics (MD) simulations were conducted with AMBER v18. The 3D-QSAR model for flavonoids with scHNE showed r² = 0.95 and q² = 0.91. High-activity compounds had hydrophobic A/A2 and C/C2 rings in the S1 subsite, with hydrogen bond donors at C5 and C7 positions of the A/A2 ring, and the C4' position of the B/B1 ring. All flavonoids except robustaflavone occupied the S1'-S2' subsites of tcHNE with decreased AutoDock binding affinities. During MD simulations, robustaflavone remained highly stable with both HNE forms. Principal Component Analysis suggested that robustaflavone binding induced structural stability in both HNE forms. Cluster analysis and free energy landscape plots showed that robustaflavone remained within the sc and tcHNE binding site throughout the 100 ns MD simulation. The robustaflavone scaffold likely inhibits both tcHNE and scHNE. It is potentially superior to sivelestat and alvelestat and can aid in developing therapeutics targeting both forms of HNE.

02 Apr 2024·Molecular cancer therapeutics

Neutrophil Elastase Remodels Mammary Tumors to Facilitate Lung Metastasis

Article

Author: Karakas, Cansu ; Rao, Xiayu ; Keyomarsi, Khandan ; Akli, Said ; Caruso, Joseph A. ; Wang, Jing ; Warma, Lucas D. ; Fowlkes, Natalie W. ; Hunt, Kelly K. ; Lulla, Amriti R. ; Watowich, Stephanie S.

Abstract:

Metastatic disease remains the leading cause of death due to cancer, yet the mechanism(s) of metastasis and its timely detection remain to be elucidated. Neutrophil elastase (NE), a serine protease secreted by neutrophils, is a crucial mediator of chronic inflammation and tumor progression. In this study, we used the PyMT model (NE+/+ and NE−/−) of breast cancer to interrogate the tumor-intrinsic and -extrinsic mechanisms by which NE can promote metastasis. Our results showed that genetic ablation of NE significantly reduced lung metastasis and improved metastasis-free survival. RNA-sequencing analysis of primary tumors indicated differential regulation of tumor-intrinsic actin cytoskeleton signaling pathways by NE. These NE-regulated pathways are critical for cell-to-cell contact and motility and consistent with the delay in metastasis in NE−/− mice. To evaluate whether pharmacologic inhibition of NE inhibited pulmonary metastasis and phenotypically mimicked PyMT NE−/− mice, we utilized AZD9668, a clinically available and specific NE inhibitor. We found AZD9668 treated PyMT-NE+/+ mice showed significantly reduced lung metastases, improved recurrence-free, metastasis-free and overall survival, and their tumors showed similar molecular alterations as those observed in PyMT-NE−/− tumors. Finally, we identified a NE-specific signature that predicts recurrence and metastasis in patients with breast cancer. Collectively, our studies suggest that genetic ablation and pharmacologic inhibition of NE reduces metastasis and extends survival of mouse models of breast cancer, providing rationale to examine NE inhibitors as a treatment strategy for the clinical management of patients with metastatic breast cancer.

News (Medical) associated with Alvelestat

13 May 2025

·www.globenewswire.com

Mereo BioPharma Reports First Quarter 2025 Financial Results and Provides Corporate Highlights

Progress continues in Phase 3 Orbit study of setrusumab in osteogenesis imperfecta (OI) Cash of $62.5 million as of March 31, 2025, expected to fund operations into 2027 LONDON, May 13, 2025 (GLOBE NEWSWIRE) -- Mereo BioPharma Group plc (NASDAQ: MREO) (“Mereo” or the “Company”), a clinical-stage biopharmaceutical company focused on rare diseases, today announced its financial results for the first quarter ended March 31, 2025, and provided recent corporate highlights. “As we close out the first quarter of 2025, we continue to anticipate that this will be an important, milestone-rich year for Mereo. The Phase 3 Orbit study of setrusumab in osteogenesis imperfecta remains on track to read-out either at the second interim analysis in mid-2025 or at the final analysis in the fourth quarter. We are continuing to invest in the pre-commercial activities for setrusumab to enable a successful launch in our European territory, following potential regulatory approvals,” said Dr. Denise Scots-Knight, Chief Executive Officer of Mereo. "Further, alvelestat is now Phase 3 ready and we are finalizing the trial start-up activities to support our ongoing partnering process. Along with our late-stage pipeline, we believe that continued close management of our cash balance will enable us to support our operations into 2027.” First Quarter 2025 Highlights, Recent Developments, and Anticipated Milestones Setrusumab (UX143) Continued progress in the two global Phase 3 studies led by our partner Ultragenyx: The randomized, placebo-controlled Phase 3 portion of the Orbit study (in patients aged 5 to 25 years) is progressing toward the second interim analysis (IA2) in mid-2025 or a final analysis in the fourth quarter of 2025. All patients have now been on therapy for at least 12 months, conduct of the study is going well and patient safety in the Phase 3 portion of the study is consistent with safety observed in the Phase 2.Patients in the Cosmic study (aged 2 to <7 years) are being treated with either setrusumab or intravenous bisphosphonates (IV-BP) therapy and will be evaluated in parallel with the Orbit interim analysis. If Orbit progresses to full study completion in the fourth quarter of 2025, Cosmic will also continue to a data readout, to align with the Orbit readout without spending alpha at the mid-year interim assessment. Continued pre-commercial activities in Europe to support potential launch, including engagement with regulatory/HTA bodies and real-world data collection efforts through the SATURN program. Alvelestat (MPH-966) In the first quarter of 2025, the European Commission granted Orphan Designation to alvelestat for the treatment of alpha-1 antitrypsin deficiency-associated lung disease (AATD-LD). This adds to existing US FDA Orphan Drug and Fast Track designations.The start-up activities for the planned single, global Phase 3 pivotal study are ongoing.The Company remains in discussion with multiple potential development and commercialization partners. First Quarter 2025 Financial Results Total research and development (“R&D”) expenses decreased by $0.1 million from $4.0 million in the first quarter of 2024 to $3.9 million in the first quarter of 2025. The decrease was primarily due to decreases of $1.2 million and $0.1 million in R&D expenses for alvelestat and etigilimab, offset by an increase of $1.3 million in R&D expenses for setrusumab. The decrease in program expenses for alvelestat was primarily due to undertaking reduced drug formulation and manufacturing activities in preparation for the Phase 3 study in the first quarter of 2025, compared to the first quarter of 2024. The increase in program expenses for setrusumab was primarily driven by amounts due under the manufacturing and supply agreement with our partner, Ultragenyx, ongoing activities related to real-world evidence programs and medical affairs activities in Europe and input into development, regulatory and manufacturing plans with Ultragenyx, who fund the global development of the program pursuant to our license and collaboration agreement. General and administrative expenses increased by $1.4 million from $5.9 million in the first quarter of 2024 to $7.3 million in the first quarter of 2025. The increase was primarily due to the recognition of a $1.7 million reduction in expenses in the first quarter of 2024 for amounts received from our depository to reimburse certain expenses incurred by us in respect of our ADR program, partially offset by a net decrease in employee-related expenses and professional fees. A reimbursement in respect of our ADR program is anticipated in 2025. Net loss for the first quarter of 2025 was $12.9 million, compared to $9.0 million during the first quarter of 2024, primarily reflecting an operating loss of $11.2 million and foreign currency translation loss. As of March 31, 2025, the Company had cash and cash equivalents of $62.5 million, compared to $69.8 million as of December 31, 2024. The Company’s guidance remains unchanged, and it continues to expect, based on current operational plans, that its existing cash and cash equivalents balance will enable it to fund its currently committed clinical trials, operating expenses, and capital expenditure requirements into 2027. This guidance does not include any potential upfront payments associated with a partnership for alvelestat or business development activity around any of the Company’s non-core programs. Total ordinary shares issued as of March 31, 2025 were 795,001,444. Total ADS equivalents as of March 31, 2025 were 159,000,288, with each ADS representing five ordinary shares of the Company. About Mereo BioPharmaMereo BioPharma is a biopharmaceutical company focused on the development of innovative therapeutics for rare diseases. The Company has two rare disease product candidates: setrusumab for the treatment of osteogenesis imperfecta (OI); and alvelestat for the treatment of severe alpha-1 antitrypsin deficiency-associated lung disease (AATD-LD). The Company’s partner, Ultragenyx Pharmaceutical, Inc., has completed enrollment in the Phase 3 portion of a pivotal Phase 2/3 study in pediatrics and young adults (5 to 25 years old) for setrusumab in OI and in the Phase 3 study in pediatric patients (2 to <7 years old). The partnership with Ultragenyx includes potential additional milestone payments of up to $245 million and royalties to Mereo on commercial sales in Ultragenyx territories. Mereo has retained EU and UK commercial rights and will pay Ultragenyx royalties on commercial sales in those territories. Setrusumab has received orphan designation for osteogenesis imperfecta from the European Commission (“EC”) and the FDA, PRIME designation from the EMA, and has Breakthrough Therapy designation and rare pediatric disease designation from the FDA. Alvelestat has received Orphan Designation for AATD from the EC and the FDA, and Fast Track designation from the FDA for AATD-LD. Following results from ASTRAEUS and ATALANTa in AATD-lung disease, the Company has aligned with the FDA and the EMA on the primary endpoints for a Phase 3 pivotal study which, if successful, could enable full approval in both the U.S. and Europe. In addition to the rare disease programs, Mereo has two oncology product candidates, etigilimab, an anti-TIGIT; and navicixizumab for the potential treatment of late-line ovarian cancer. Navicixizumab has been partnered with Feng Biosciences, Inc. in a global licensing agreement that includes milestone payments and royalties. Mereo has also entered into an exclusive global license agreement with ReproNovo SA, a reproductive medicine company, for the development and commercialization of leflutrozole, a non-steroidal aromatase inhibitor. Forward-Looking StatementsThis press release contains “forward-looking statements” that involve substantial risks and uncertainties. All statements other than statements of historical fact contained herein are forward-looking statements within the meaning of Section 27A of the United States Securities Act of 1933, as amended, and Section 21E of the United States Securities Exchange Act of 1934, as amended. Forward-looking statements usually relate to future events and anticipated revenues, earnings, cash flows or other aspects of our operations or operating results. Forward-looking statements are often identified by the words “believe,” “expect,” “anticipate,” “plan,” “intend,” “foresee,” “should,” “would,” “could,” “may,” “estimate,” “outlook” and similar expressions, including the negative thereof. The absence of these words, however, does not mean that the statements are not forward-looking. These forward-looking statements are based on the Company’s current expectations, beliefs and assumptions concerning future developments and business conditions and their potential effect on the Company. While management believes that these forward-looking statements are reasonable as and when made, there can be no assurance that future developments affecting the Company will be those that it anticipates. All of the Company’s forward-looking statements involve known and unknown risks and uncertainties some of which are significant or beyond its control and assumptions that could cause actual results to differ materially from the Company’s historical experience and its present expectations or projections. Such risks and uncertainties include, among others, the uncertainties inherent in the clinical development process; the Company’s reliance on third parties to conduct and provide funding for its clinical trials; the Company’s dependence on enrollment of patients in its clinical trials; and the Company’s dependence on its key executives. You should carefully consider the foregoing factors and the other risks and uncertainties that affect the Company’s business, including those described in the “Risk Factors” section of its Annual Report on Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in the Company’s subsequent filings with the Securities and Exchange Commission. The Company wishes to caution you not to place undue reliance on any forward-looking statements, which speak only as of the date hereof. The Company undertakes no obligation to publicly update or revise any of our forward-looking statements after the date they are made, whether as a result of new information, future events or otherwise, except to the extent required by law. Mereo BioPharma Contacts: Mereo +44 (0)333 023 7300Denise Scots-Knight, Chief Executive Officer Christine Fox, Chief Financial Officer Burns McClellan (Investor Relations Adviser to Mereo) +01 646 930 4406Lee Roth Investors investors@mereobiopharma.com MEREO BIOPHARMA GROUP PLCCONDENSED CONSOLIDATED BALANCE SHEETS(In thousands, except per share amounts)(Unaudited) March 31, December 31, 2025 2024 Assets Current assets: Cash and cash equivalents $62,483 $69,802 Prepaid expenses and other current assets 2,519 2,175 Research and development incentives receivables 1,897 2,786 Total current assets 66,899 74,763 Property and equipment, net 247 257 Operating lease right-of-use assets, net 622 727 Intangible assets, net 554 643 Total assets $68,322 $76,390 Liabilities Current liabilities: Accounts payable $2,924 $2,440 Accrued expenses 2,932 4,071 Convertible loan notes – current — 5,535 Operating lease liabilities – current 747 707 Other current liabilities 894 1,095 Total current liabilities 7,497 13,848 Warrant liabilities – non-current 419 821 Operating lease liabilities – non-current — 187 Other non-current liabilities 325 565 Total liabilities $8,241 $15,421 Shareholders’ Equity Ordinary shares, par value £0.003 per share; 795,001,444 shares issued at March 31, 2025 (December 31, 2024: 775,728,034). $3,132 $3,059 Additional paid-in capital 544,266 539,642 Accumulated deficit (472,027) (462,883)Accumulated other comprehensive loss (15,290) (18,849)Total shareholders’ equity 60,081 60,969 Total liabilities and shareholders’ equity $68,322 $76,390 MEREO BIOPHARMA GROUP PLCCONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS(In thousands, except per share amounts)(Unaudited) Three Months Ended March 31, 2025 2024 Operating expenses: Research and development $(3,930) $(3,994)General and administrative (7,272) (5,906)Loss from operations (11,202) (9,900)Other income/(expenses) Interest income 659 617 Interest expense (180) (310)Changes in the fair value of warrants 416 (448)Foreign currency transaction (loss)/gain, net (2,765) 613 Benefit from research and development tax credit 185 477 Net loss before income tax (12,887) (8,951)Income tax benefit — — Net loss $(12,887) $(8,951) Loss per share – basic and diluted $(0.02) $(0.01)Weighted average shares outstanding – basic and diluted 784,279,387 700,263,490 Net loss $(12,887) $(8,951)Other comprehensive income/(loss) – Foreign currency translation adjustments, net of tax 3,559 (798)Total comprehensive loss $(9,328) $(9,749)

Fast TrackPhase 3Orphan DrugFinancial StatementLicense out/in

12 Jan 2025

·www.globenewswire.com

Mereo BioPharma Provides Update on Lead Clinical Programs

Orbit Phase 3 study of setrusumab in osteogenesis imperfecta continuing to planned second interim analysis, expected in mid-2025 Alvelestat, for Alpha-1 Antitrypsin Deficiency-associated Lung Disease, receives positive EMA opinion on European Orphan Designation Application; European Commission expected to issue final decision in first quarter 2025 LONDON, Jan. 12, 2025 (GLOBE NEWSWIRE) -- Mereo BioPharma Group plc (NASDAQ: MREO) (“Mereo” or the “Company”), a clinical-stage biopharmaceutical company focused on rare diseases, today provided an update on its lead clinical programs, setrusumab, a monoclonal antibody in Phase 3 clinical development for the treatment of Osteogenesis Imperfecta (OI) through a partnership with Ultragenyx Pharmaceutical, Inc. (Ultragenyx) and alvelestat, an oral neutrophil elastase inhibitor being studied for the treatment of alpha-1 antitrypsin deficiency-associated lung disease (AATD-LD). The Company also reiterated its previous cash runway guidance that its current cash and cash equivalents are expected to fund operations into 2027, through multiple key inflection points. “Based on the highly promising data from completed studies of setrusumab in OI, including the Phase 2 portion of the Orbit Study, we remain confident in the potential of setrusumab to become the standard-of-care in OI. We look forward to the second interim analysis expected mid-year as we continue our launch readiness activities in the key European markets,” said Dr. Denise Scots-Knight, Chief Executive Officer of Mereo BioPharma. “Additionally, EU Orphan Designation, which follows the granting of both Orphan Drug and Fast Track Designations from the FDA in the U.S., is another important milestone in our ongoing partnering process and our efforts to bring alvelestat to patients worldwide, including earlier stage patients who are not currently eligible for augmentation therapy in many countries. With our cash runway into 2027, we continue to be in a strong position to execute on our key milestones through 2025.” Setrusumab (UX143) As announced by the Company’s partner, Ultragenyx, the Phase 3 Orbit Study of setrusumab in OI is continuing to dose patients and progressing towards the planned second interim analysis expected in mid-2025, with a potential final analysis in the fourth quarter of 2025. Additionally, treatment is continuing in Cosmic, an open-label Phase 3 study evaluating setrusumab against intravenous bisphosphonate therapy in patients aged 2 to <7 years. Data from the Cosmic study will be evaluated in parallel with the Orbit interim and final analyses. Alvelestat (MPH-966) The European Medicines Agency (EMA)’s Committee for Orphan Medicinal Products (COMP) has issued a positive opinion on the Company’s application for Orphan Designation for alvelestat. The COMP recommendation has been provided to the European Commission, which is expected to issue a final decision on the Orphan Designation in the first quarter of 2025. Alvelestat previously received Orphan Drug Designation and Fast Track Designation from the U.S. FDA in 2021 and 2022, respectively. European Orphan Designation is awarded to therapeutic candidates targeting the treatment, prevention or diagnosis of life-threatening or chronically debilitating diseases with a prevalence of fewer than 5 in 10,000 people in the European Union which provide a significant benefit over available therapies, or for which no approved therapies exist. Therapeutics receiving EU Orphan Designation are eligible for ten years of marketing exclusivity upon approval, as well as fee reductions for various centralized activities including the Marketing Authorization Application, inspections and protocol assistance. Individual EU Member States also provide specific incentives to support the development, review and availability of Orphan Medicinal Products at the time of HTA evaluations and Pricing and Reimbursement negotiations. About Mereo BioPharma Mereo BioPharma is a biopharmaceutical company focused on the development of innovative therapeutics for rare diseases. The Company has two rare disease product candidates: setrusumab for the treatment of osteogenesis imperfecta (OI); and alvelestat, primarily for the treatment of severe alpha-1 antitrypsin deficiency-associated lung disease (AATD-LD). The Company’s partner, Ultragenyx Pharmaceutical, Inc., has completed enrollment in the Phase 3 portion of a pivotal Phase 2/3 study in pediatrics and young adults (5 to 25 years old) for setrusumab in OI and in the Phase 3 study in pediatric patients (2 to <7 years old) in the first half of 2024. The partnership with Ultragenyx includes potential additional milestone payments of up to $245 million and royalties to Mereo on commercial sales in Ultragenyx territories. Mereo has retained EU and UK commercial rights and will pay Ultragenyx royalties on commercial sales in those territories. Setrusumab has received orphan designation for osteogenesis imperfecta from the EMA and FDA, PRIME designation from the EMA, and Breakthrough Therapy designation and rare pediatric disease designation from the FDA. Alvelestat has received U.S. Orphan Drug Designation for the treatment of AATD and Fast Track designation from the FDA. Following results from ASTRAEUS and ATALANTa in AATD-lung disease, the Company has aligned with the FDA and the EMA on the primary endpoints for a Phase 3 pivotal study which, if successful, could enable full approval in both the U.S. and Europe. In addition to the rare disease programs, Mereo has two oncology product candidates, etigilimab, an anti-TIGIT; and navicixizumab for the potential treatment of late-line ovarian cancer. Navicixizumab has been partnered with Feng Biosciences, Inc. in a global licensing agreement that includes milestone payments and royalties. Mereo has also entered into an exclusive global license agreement with ReproNovo SA, a reproductive medicine company, for the development and commercialization of leflutrozole, a non-steroidal aromatase inhibitor. Forward-Looking Statements This press release contains “forward-looking statements” that involve substantial risks and uncertainties. All statements other than statements of historical fact contained herein are forward-looking statements within the meaning of Section 27A of the United States Securities Act of 1933, as amended, and Section 21E of the United States Securities Exchange Act of 1934, as amended. Forward-looking statements usually relate to future events and anticipated revenues, earnings, cash flows or other aspects of our operations or operating results. Forward-looking statements are often identified by the words “believe,” “expect,” “anticipate,” “plan,” “intend,” “foresee,” “should,” “would,” “could,” “may,” “estimate,” “outlook” and similar expressions, including the negative thereof. The absence of these words, however, does not mean that the statements are not forward-looking. These forward-looking statements are based on the Company’s current expectations, beliefs and assumptions concerning future developments and business conditions and their potential effect on the Company. While management believes that these forward-looking statements are reasonable as and when made, there can be no assurance that future developments affecting the Company will be those that it anticipates. All of the Company’s forward-looking statements involve known and unknown risks and uncertainties some of which are significant or beyond its control and assumptions that could cause actual results to differ materially from the Company’s historical experience and its present expectations or projections. Such risks and uncertainties include, among others, the uncertainties inherent in the clinical development process; the Company’s reliance on third parties to conduct and provide funding for its clinical trials; the Company’s dependence on enrollment of patients in its clinical trials; and the Company’s dependence on its key executives. You should carefully consider the foregoing factors and the other risks and uncertainties that affect the Company’s business, including those described in the “Risk Factors” section of its Annual Report on Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in the Company’s subsequent filings with the Securities and Exchange Commission. The Company wishes to caution you not to place undue reliance on any forward-looking statements, which speak only as of the date hereof. The Company undertakes no obligation to publicly update or revise any of our forward-looking statements after the date they are made, whether as a result of new information, future events or otherwise, except to the extent required by law. Mereo BioPharma Contacts: Mereo +44 (0)333 023 7300Denise Scots-Knight, Chief Executive Officer Christine Fox, Chief Financial Officer Burns McClellan (Investor Relations Adviser to Mereo) +01 646 930 4406Lee Roth Investors investors@mereobiopharma.com

Phase 3Orphan DrugFast TrackLicense out/inBreakthrough Therapy

07 Jan 2025

·www.globenewswire.com

Mereo BioPharma to Present at the 43rd Annual J.P. Morgan Healthcare Conference

LONDON, Jan. 07, 2025 (GLOBE NEWSWIRE) -- Mereo BioPharma Group plc (NASDAQ: MREO) (“Mereo” or the “Company”), a clinical-stage biopharmaceutical company focused on rare diseases, today announced that Dr. Denise Scots-Knight, Chief Executive Officer, will present at the 43rd Annual J.P. Morgan Healthcare Conference on Thursday, January 16, 2025, at 8:15am PT / 04:15pm GMT. A live audio webcast of the presentation can be accessed through the Investors section of the Company’s website at www.mereobiopharma.com/investors. An archived replay of the webcast will be available on the Company’s website for two weeks following the live event. About Mereo BioPharma Mereo BioPharma is a biopharmaceutical company focused on the development of innovative therapeutics for rare diseases. The Company has two rare disease product candidates, setrusumab for the treatment of osteogenesis imperfecta (OI) and alvelestat primarily for the treatment of severe alpha-1 antitrypsin deficiency-associated lung disease (AATD-LD). The Company’s partner, Ultragenyx Pharmaceutical, Inc., has completed enrollment in the Phase 3 portion of a pivotal Phase 2/3 study in pediatrics and young adults (5 to 25 years old) for setrusumab in OI and in the Phase 3 study in pediatric patients (2 to <7 years old) in the first half of 2024. The partnership with Ultragenyx includes potential additional milestone payments of up to $245 million and royalties to Mereo on commercial sales in Ultragenyx territories. Mereo has retained EU and UK commercial rights and will pay Ultragenyx royalties on commercial sales in those territories. Setrusumab has received orphan designation for osteogenesis imperfecta from the EMA and FDA, PRIME designation from the EMA, and Breakthrough Therapy designation and rare pediatric disease designation from the FDA. Alvelestat has received U.S. Orphan Drug Designation for the treatment of AATD and Fast Track designation from the FDA. Following results from ASTRAEUS and ATALANTa in AATD-lung disease, the Company has aligned with the FDA and the EMA on the primary endpoints for a Phase 3 pivotal study which if successful could enable full approval in both the U.S. and Europe. In addition to the rare disease programs, Mereo has two oncology product candidates, etigilimab, an anti-TIGIT, and navicixizumab for the potential treatment of late line ovarian cancer. Navicixizumab has been partnered with Feng Biosciences Inc. in a global licensing agreement that includes milestone payments and royalties. Mereo has also entered into an exclusive global license agreement with ReproNovo SA, a reproductive medicine company, for the development and commercialization of leflutrozole, a non-steroidal aromatase inhibitor. Forward-Looking Statements This press release contains “forward-looking statements” that involve substantial risks and uncertainties. All statements other than statements of historical fact contained herein are forward-looking statements within the meaning of Section 27A of the United States Securities Act of 1933, as amended, and Section 21E of the United States Securities Exchange Act of 1934, as amended. Forward-looking statements usually relate to future events and anticipated revenues, earnings, cash flows or other aspects of our operations or operating results. Forward-looking statements are often identified by the words “believe,” “expect,” “anticipate,” “plan,” “intend,” “foresee,” “should,” “would,” “could,” “may,” “estimate,” “outlook” and similar expressions, including the negative thereof. The absence of these words, however, does not mean that the statements are not forward-looking. These forward-looking statements are based on the Company’s current expectations, beliefs and assumptions concerning future developments and business conditions and their potential effect on the Company. While management believes that these forward-looking statements are reasonable as and when made, there can be no assurance that future developments affecting the Company will be those that it anticipates. All of the Company’s forward-looking statements involve known and unknown risks and uncertainties some of which are significant or beyond its control and assumptions that could cause actual results to differ materially from the Company’s historical experience and its present expectations or projections. Such risks and uncertainties include, among others, the uncertainties inherent in the clinical development process; the Company’s reliance on third parties to conduct and provide funding for its clinical trials; the Company’s dependence on enrollment of patients in its clinical trials; and the Company’s dependence on its key executives. You should carefully consider the foregoing factors and the other risks and uncertainties that affect the Company’s business, including those described in the “Risk Factors” section of its Annual Report on Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in the Company’s subsequent filings with the Securities and Exchange Commission. The Company wishes to caution you not to place undue reliance on any forward-looking statements, which speak only as of the date hereof. The Company undertakes no obligation to publicly update or revise any of our forward-looking statements after the date they are made, whether as a result of new information, future events or otherwise, except to the extent required by law. Mereo BioPharma Contacts: Mereo +44 (0)333 023 7300Denise Scots-Knight, Chief Executive Officer Christine Fox, Chief Financial Officer Burns McClellan (Investor Relations Adviser to Mereo) +01 646 930 4406Lee Roth Investors investors@mereobiopharma.com

Phase 3Orphan DrugLicense out/inFast TrackBreakthrough Therapy

100 Deals associated with Alvelestat

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Indication	Highest Phase	Country/Location	Organization	Date
Graft vs Host Disease	Phase 2	United States	Mereo BioPharma Group Plc	01 Sep 2021
Hematologic Neoplasms	Phase 2	United States	Mereo BioPharma Group Plc	01 Sep 2021
COVID-19	Phase 2	United States	Mereo BioPharma Group Plc	25 Jan 2021
COVID-19 respiratory infection	Phase 2	United States	Mereo BioPharma Group Plc	25 Jan 2021
Alpha 1-Antitrypsin Deficiency	Phase 2	United States	Mereo BioPharma Group Plc	29 Oct 2018
Alpha 1-Antitrypsin Deficiency	Phase 2	Belgium	Mereo BioPharma Group Plc	29 Oct 2018
Alpha 1-Antitrypsin Deficiency	Phase 2	Canada	Mereo BioPharma Group Plc	29 Oct 2018
Alpha 1-Antitrypsin Deficiency	Phase 2	Denmark	Mereo BioPharma Group Plc	29 Oct 2018
Alpha 1-Antitrypsin Deficiency	Phase 2	Poland	Mereo BioPharma Group Plc	29 Oct 2018
Alpha 1-Antitrypsin Deficiency	Phase 2	Spain	Mereo BioPharma Group Plc	29 Oct 2018

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03679598 (ATALANTa, CTgov)	Phase 2	Pulmonary Disease, Chronic Obstructive \| Alpha 1-Antitrypsin Deficiency	63	Alvelestat (MPH966) (Alvelestat (MPH966))	ztjmaerqlm(serkgwhyje) = yivcdgyleb flncvwdaaj (usnjzitdrh, 27.8489) View more	-	09 Jul 2024
				Placebo (Placebo)	ztjmaerqlm(serkgwhyje) = kzovgibift flncvwdaaj (usnjzitdrh, 29.2973) View more
NCT03679598 (ATS2024) Manual	Phase 2	Alpha 1-Antitrypsin Deficiency	63	Alvelestat 120mg	dmhhjnjnyu(hygifnlquz) = The most common were headache/migraines in alvelestat and worsening of COPD symptoms in the placebo group. Two participants in the alvelestat group withdrew due to headache. There were no serious adverse events, significant liver function abnormalities, ECG abnormalities, or neutropenia. nbkrwfyuce (txoreginlj )	Positive	19 May 2024
				Placebo
NCT04539795 (COSTA, Corporate Publications) Manual	Phase 1/2	COVID-19	15	Alvelestat	pqdgzbagwh(xsxgvjtmuu) = hwkjufekqg hodjsglvkp (jgksrkjgha ) View more	Positive	22 Dec 2021
				Placebo	sqnsothcnx(oayikcidfq) = wqueyoquea gjeodloyox (icvliokfnu ) View more
NCT02597101 (CTgov)	Phase 2	Diabetes Mellitus, Type 2 \| Insulin Resistance \| Obesity	14	placebo+metformin+saxagliptin (Placebo)	infdlodnjl(xjqrjgjisr) = gojjejrrci ukhdqvgzed (axyknzghct, 3.7) View more	-	13 May 2021
				AZD9668+metformin+saxagliptin (AZD9668)	infdlodnjl(xjqrjgjisr) = mssxqvfcap ukhdqvgzed (axyknzghct, 3.5) View more
NCT01023516 (CTgov)	Phase 2	Pulmonary Disease, Chronic Obstructive	615	AZD9668 (60 mg AZD9668)	mgwjdtwhvh(zasjtooomb) = bvszhvgudc qvbwgqbsrb (qloulfjgcr, 0.539) View more	-	03 Aug 2012
				Placebo (Placebo)	mgwjdtwhvh(zasjtooomb) = kwkjzclcua qvbwgqbsrb (qloulfjgcr, 0.519) View more
NCT00949975 (CTgov)	Phase 2	Pulmonary Disease, Chronic Obstructive	838	AZD9668 (5 mg AZD9668)	pqzsxopzoo(fuweqyaefr) = ibsjlgmdks mjdrmdgvai (xgxcacbwnh, 0.471) View more	-	03 Aug 2012
				AZD9668 (20 mg AZD9668)	pqzsxopzoo(fuweqyaefr) = czpyaemzti mjdrmdgvai (xgxcacbwnh, 0.468) View more
NCT00769119 (NEPAL, CTgov)	Phase 2	Bronchiectasis	38	AZD9668 (AZD9668)	zdpkuaxsrd(oykyuobtua) = uhyjxvvhnr kpexjjtpir (vberrgrhct, dizvcfkpui - tqpyqikkbr) View more	-	25 Jul 2012
				Placebo (Placebo)	zdpkuaxsrd(oykyuobtua) = pbtfnmpdpm kpexjjtpir (vberrgrhct, pdcitvcsig - mosvdcogrw) View more
NCT01054170 (CTgov)	Phase 2	Pulmonary Disease, Chronic Obstructive	52	AZD9668 (AZD9668)	ypmfdmjzau(glvcilezys) = ggapiadwul vijfpavqbg (rljngwxwxm, 0.021) View more	-	25 Jul 2012
				Placebo (Placebo)	ypmfdmjzau(glvcilezys) = qelznmjmla vijfpavqbg (rljngwxwxm, 0.017) View more
NCT00757848 (INCA, CTgov)	Phase 2	Cystic Fibrosis	56	AZD9668 (AZD9668)	akmxwzcvnj(jkzgvzpziv) = iuhhctscsk oxfiujovtj (aherdnachj, pbyzbmqsxc - egwbddmnbm) View more	-	25 Jul 2012
				AZD9668 Placebo equivalent (Placebo)	akmxwzcvnj(jkzgvzpziv) = mvrdpyzrki oxfiujovtj (aherdnachj, dnnovwymbh - qxxlwkhbch) View more
NCT00703391 (CTgov)	Phase 2	Pulmonary Disease, Chronic Obstructive	18	AZD9668 (AZD9668)	lwxbfmngrg = ocvxqvmzhi zkaeeprims (bjzqfneraj, dtsykmqqes - zdzwjmchvx) View more	-	29 Dec 2010
				placebo (Placebo)	lwxbfmngrg = xexkgizcvr zkaeeprims (bjzqfneraj, gapcatqtsf - zhnzzbykef) View more

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