New data at ASH underscore the potential for durable, clinically important responses with momelotinib for myelofibrosis patients

• 48-week data from MOMENTUM phase III clinical trial show momelotinib maintained total symptom response, transfusion independence and splenic response in the majority of patients who responded to treatment during first 24 weeks
• Additional analyses from MOMENTUM suggest that transfusion independence at week 24 was associated with overall survival

GSK plc (LSE/NYSE:GSK) today announced new 48-week data from the MOMENTUM phase III trial that showed a majority of patients treated with investigational momelotinib maintained their responses across key clinical measures including Total Symptom Score (TSS), Transfusion Independence (TI) rate, and Splenic Response Rate (SRR) in myelofibrosis patients previously treated with an approved Janus kinase (JAK) inhibitor. Additionally, new analyses from MOMENTUM showed that TI response with momelotinib at week 24 was associated with overall survival. These data were presented at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition (10-13 December) in New Orleans.

Hesham Abdullah, Senior Vice President, Global Head of Oncology Development, GSK, said: “Myelofibrosis patients have significant medical needs including progressive anemia resulting from the disease and often exacerbated by currently approved treatments. The data presented today reinforce the potential of momelotinib as a treatment option with a favorable impact on myelofibrosis symptoms and spleen volume, as well as on blood transfusions due to anemia.”

MOMENTUM is a global, randomized, double-blind phase III clinical trial of momelotinib (MMB) versus danazol (DAN) in patients with myelofibrosis who were symptomatic and anemic and had been previously treated with an approved JAK inhibitor. The study was designed to evaluate the safety and efficacy of momelotinib for the treatment and reduction of the key manifestations of the disease: constitutional symptoms, blood transfusions (due to anemia) and enlarged spleen. Patients were randomized at 2:1 to receive either momelotinib or danazol (n=130 and n=65, respectively). After 24 weeks of treatment, patients on danazol were allowed to crossover to receive momelotinib. Early crossover to momelotinib was available for confirmed splenic progression.

Primary analysis at week 24 met the primary endpoint of TSS reduction of ≥50% over the 28 days immediately before the end of week 24 compared to baseline TSS, using the Myelofibrosis Symptom Assessment Form. It also met key secondary endpoints including TI rate for ≥12 weeks immediately before the end of week 24 with hemoglobin levels ≥8 g/dL and SRR based on splenic volume reduction of ≥35% at week 24 from baseline.

48-week follow-up data from MOMENTUM presented at ASH demonstrated the following (oral presentation #627):

In MOMENTUM, the most common Grade 3 or greater treatment emergent adverse events in the open-label period, similar to the double-blind period, were thrombocytopenia (9% for the continuous momelotinib treatment arm and 15% for the danazol to momelotinib treatment arm) and anemia (9% for the continuous momelotinib treatment arm and 2% for the danazol to momelotinib treatment arm). Additionally, these efficacy and safety results in patients with thrombocytopenia were consistent with the overall population.

An additional analysis from the MOMENTUM clinical trial evaluated the impact of TI response on overall survival (abstract #3028). As previously presented, patients receiving treatment with momelotinib were more likely to achieve transfusion independence during the study period than patients treated with danazol (TI response at week 24 of 31% and 20% for the momelotinib and danazol arms, respectively; non-inferiority p=0.0064). Momelotinib patients were also less likely to require a transfusion during the study period (35% of momelotinib patients had zero units transfused compared to 17% of danazol patients; odds ratio=2.7; p=0.0107), and more likely to reduce transfusion burden. Data presented at ASH with additional survival follow up suggests that TI response with momelotinib at week 24 is associated with overall survival (HR=0.27 for TI vs. non-TI; CI 95% 0.09, 0.80) compared to patients who were not TI.

A New Drug Application and Marketing Authorization Application for momelotinib is currently under review with the US Food and Drug Administration (FDA) and European Medicines Agency (EMA), respectively. Momelotinib is not currently approved in any market.

About momelotinib

Momelotinib is an investigational oral treatment for myelofibrosis. Momelotinib not only inhibits the Janus kinase (JAK) 1 signalling pathway and JAK2 signalling pathways, but also activin A receptor type I (ACVR1).^1,2,3,4 Inhibition of JAK1 and JAK2 may improve constitutional symptoms and splenomegaly.^1,2,4 Additionally, direct inhibition of ACVR1 leads to a decrease in circulating hepcidin, which is often elevated in myelofibrosis and contributes to anemia.^1,2,3,4

About myelofibrosis

Myelofibrosis is a rare and potentially fatal cancer characterized by the build-up of excessive scar tissue in the bone marrow, which interferes with the production of healthy blood cells and can lead to: severe low blood counts, including anemia and thrombocytopenia; constitutional symptoms such as weakness and fatigue; and splenomegaly or an enlarged spleen.^5,6,7 Myelofibrosis affects about 1 in 500,000 people worldwide.⁸ At diagnosis, approximately 40% of patients are anemic and nearly all myelofibrosis patients will eventually develop anemia.^9,10,11 Patients will often require blood transfusions, and more than 30% will discontinue treatment due to anemia.¹² Anemia and transfusion dependence are strongly correlated with poor prognosis, reduced quality of life and shortened survival.^{13,14,15,16,17,18,19,20,21}

GSK in oncology

GSK is focused on maximizing patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, tumor cell targeting therapies and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilizing modalities such as small molecules, antibodies, and antibody-drug conjugates, either alone or in combination.

About GSK

GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com/company.

Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described in the Company's Annual Report on Form 20-F for 2021, GSK’s Q3 Results for 2022 and any impacts of the COVID-19 pandemic.

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1</sup> Chifotides, H.T., Bose, P. & Verstovsek, S. Momelotinib: an emerging treatment for myelofibrosis patients with anemia. J Hematol Oncol 15, 7 (2022). https://doi.org/10.1186/s13045-021-01157-4.

² Verstovsek S, et al. MOMENTUM: momelotinib vs danazol in patients with myelofibrosis previously treated with JAKi who are symptomatic and anemic. Future Oncol. 2021;17(12):1449-1458. https://doi.org/10.2217/fon-2020-1048.

³ Asshoff M, et al. Momelotinib inhibits ACVR1/ALK2, decreases hepcidin production, and ameliorates anemia of chronic disease in rodents. Blood. 2017;129(13):1823-1830.

⁴ Oh S, et al. ACVR1/JAK1/JAK2 inhibitor momelotinib reverses transfusion dependency and suppresses hepcidin in myelofibrosis phase 2 trial. Blood Adv. 2020;4(18):4282-4291.

⁵ NIH National Library of Medicine. Primary Myelofibrosis. September 2014. Accessed 5 August 2022. https://medlineplus.gov/genetics/condition/primary-myelofibrosis/.

⁶ MPN Research Foundation. Primary Myelofibrosis (PMF). 2021. Accessed August, 2022. http://www.mpnresearchfoundation.org/primary-myelofibrosis-pmf/.

⁷ National Organization for Rare Disorders (NORD). Primary Myelofibrosis. 2018. Accessed 9 August 2022. https://rarediseases.org/rare-diseases/primary-myelofibrosis/.

⁸ Mehta, J., Wang, H., Iqbal S.U., Mesa, R. Epidemiology of myeloproliferative neoplasms in the United States. Leukemia & Lymphoma. 2014;55(3):595-600.

⁹ Bose P, et al. Curr Hematol Malign Rep. 2018;13:164-172. doi: https://doi.org/10.3109/10428194.2013.813500.

¹⁰ Scherber, R.M., Mesa, R. Management of challenging myelofibrosis after JAK inhibitor failure and/or progression. Blood Rev. 2020;42:100716. https://doi.org/10.1016/j.blre.2020.100716.

¹¹ Tefferi A. Clinical manifestations and diagnosis of primary myelofibrosis. Accessed March 7, 2022.

¹² Palandri, F., Palumbo, G.A., Elli, E.M. et al. Ruxolitinib discontinuation syndrome: incidence, risk factors, and management in 251 patients with myelofibrosis. Blood Cancer J. 11, 4 (2021). https://doi.org/10.1038/s41408-020-00392-1.

¹³ Naymagon, L., Mascarenhas, J. Myelofibrosis-Related Anemia: Current and Emerging Therapeutic Strategies. HemaSphere. 2017;1(1):e1. doi: 10.1097/HS9.0000000000000001.

¹⁴ Tefferi A. Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management. Am J Hematol. 2021;96(1):145-162. https://doi.org/10.1002/ajh.26050.

¹⁵ Rumi E, et al. The Genetic Basis of Primary Myelofibrosis and Its Clinical Relevance. Int J Mol Sci. 2020;21(23):8885. https://doi.org/10.3390/ijms21238885.

¹⁶ How J, Hobbs GS. A Practical Guide for Using Myelofibrosis Prognostic Models in the Clinic. J Natl Compr Canc Netw. 2020;18(9):1271-1278. https://doi.org/10.6004/jnccn.2020.7557.

¹⁷ QxMD. DIPSS prognosis in myelofibrosis. Accessed September 12, 2022. https://qxmd.com/calculate/calculator_187/dipss-prognosis-in-myelofibrosis.

¹⁸ QxMD. DIPSS plus score for prognosis of myelofibrosis. Accessed September 12, 2022.

¹⁹ Tefferi A, et al. Use of the Functional Assessment of Cancer Therapy--anemia in persons with myeloproliferative neoplasm-associated myelofibrosis and anemia. Clin Ther. 2014;36(4):560-566. https://doi.org/10.1016/j.clinthera.2014.02.016.

²⁰ Nicolosi M, et al. Sex and degree of severity influence the prognostic impact of anemia in primary myelofibrosis: analysis based on 1109 consecutive patients. Leukemia. 2018;32(5):1254-1258. https://doi.org/10.1038/s41375-018-0028-x.

²¹ Elena C, et al. Red blood cell transfusion-dependency implies a poor survival in primary myelofibrosis irrespective of IPSS and DIPSS. Haematologica. 2011;96(1):167-170. https://doi.org/10.3324/haematol.2010.031831.

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