AJ1-11095 / Ajax Therap, Schrodinger, Eli Lilly - LARVOL DELTA

RESULTS OF AJX-101, A PHASE 1 CLINICAL TRIAL OF THE TYPE II JAK2 INHIBITOR AJ1-11095, IN PATIENTS WITH MYELOFIBROSIS WHO HAVE BEEN FAILED BY A TYPE I JAK2 INHIBITOR (EHA 2026) - P1 | "Results In the dose escalation phase, 23 patients (ages 47-87y,16M/7F; 16 JAK2 V617F, 6 CALR, 2 MPL W515K/L mutations; median 2 prior therapies (range 1-7), median 6.1y from diagnosis; all with prior ruxolitinib exposure, 8 with momelotinib) enrolled across 6 dose levels: 25 (n=3), 50 (n=3), 75 (n=6), 100 (n=6), and 125 mg (n=5) orally once daily. Summary/Conclusion The first-in-class type II JAK2 inhibitor AJ1-11095 induces symptomatic improvement, spleen volume reduction, and decrease in mutant clone size in most patients with MF previously treated with type I JAK2 inhibitors. The 75 mg QD dose was selected for initial dose expansion."

Clinical • First-in-human • P1 data • Myelofibrosis • Thrombocytopenia • CALR • TYK2

A Phase 1 Study of LY5830966 in Participants With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) Who Have Been Failed by a Type I JAK2 Inhibitor (JAK2i) (clinicaltrials.gov) - P1 | N=256 | Recruiting | Sponsor: Ajax Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company | N=76 ➔ 256 | Trial completion date: Feb 2027 ➔ Dec 2028 | Trial primary completion date: Oct 2026 ➔ Jun 2027

Enrollment change • First-in-human • Trial completion date • Trial primary completion date • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytosis • JAK2

Type II JAK2 Inhibitor Gets Off to a Strong Start. (PubMed, Cancer Discov) - "AJ1-11095, a type II JAK2 inhibitor being developed for myelofibrosis, led to impressive clinical responses in a recent phase I study, suggesting that the drug, and perhaps the rest of its still-investigational class, could prove better than currently approved type I JAK2 inhibitors."

Journal • Myelofibrosis

Eli Lilly and Company…announced new data from the Phase 1 AJX-101 study showing that its investigational type II JAK2 inhibitor (AJ1-11095) demonstrated an encouraging safety profile and promising clinical activity in patients with myelofibrosis who have been failed by a type I JAK2 inhibitor (Eli Lilly Press Release) - "These data will be highlighted in an oral presentation at the 2026 European Hematology Association (EHA) Annual Meeting....The trial enrolled 23 patients across five dose levels (25, 50, 75, 100, and 125 mg once daily) in its dose escalation phase.....AJ1-11095 demonstrated responses across the standard efficacy endpoints of spleen volume reduction and symptom improvement. The SVR35 rate, a reduction in spleen volume of at least 35%, was observed as best response in 70% of patients....Among the 17 patients who reached week 24 of treatment, 59% saw a reduction of 20% or greater and 35% saw a reduction of 50% or greater, including JAK2, MPL, and CALR type 1 and type 2 mutations."

CALR • P1 data • Myelofibrosis

Lilly to spotlight growing hematology portfolio at 2026 European Hematology Association (EHA) Annual Meeting (Eli Lilly Press Release) - "Positive results from the Phase 3 BRUIN CLL-322 study comparing time-limited pirtobrutinib plus venetoclax and rituximab versus venetoclax and rituximab in patients with relapsed or refractory CLL/SLL will be highlighted in a late-breaking oral presentation...Ajax Therapeutics will present the first clinical data from the Phase 1 AJX-101 study evaluating AJ1-11095, an investigational first-in-class type II JAK2 inhibitor, in patients with myelofibrosis who have been failed by a type I JAK2 inhibitor. Kelonia Therapeutics will present additional correlative data from the Phase 1 inMMyCAR study of an investigational anti-B-cell maturation antigen (BCMA) targeted in vivo CAR-T therapy in patients with relapsed and refractory multiple myeloma. Both proposed acquisitions by Lilly are pending transaction closes."

Late-breaking abstract • P1 data • P3 data • Chronic Lymphocytic Leukemia • Multiple Myeloma • Myelofibrosis • Small Lymphocytic Lymphoma

Ajax Therapeutics Announces Oral Presentation of Clinical Results from AJX-101, a Phase I study of AJ1-11095, a First-in-Class Type II JAK2 Inhibitor, at the European Hematology Society (EHA) 2026 Congress (The Manila Times) - "Ajax Therapeutics Announces Oral Presentation of Clinical Results from AJX-101, a Phase I study of AJ1-11095, a First-in-Class Type II JAK2 Inhibitor, at the European Hematology Society (EHA) 2026 Congress. The oral presentation will include results from the Phase 1 clinical trial, AJX-101, an open-label, multi-center study designed to evaluate the safety, tolerability and preliminary efficacy of AJ1-11095. The study has enrolled patients in the U.S. and Europe with Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) who have been failed by a type I JAK2 Inhibitor. (NCT identifier: NCT06343805)."

P1 data • Myelofibrosis • Polycythemia Vera

Eli Lilly to buy Ajax Therapeutics for up to $2.3 billion in blood cancer bet (The Economic Times) - "Ajax's lead asset, AJ1-11095, is an experimental once-daily oral treatment that is in early-stage testing for previously treated patients with myelofibrosis - - a rare, chronic blood cancer where scar tissue builds ⁠up in ‌the bone marrow, , disrupting normal blood cell production."

M&A • Myelofibrosis

Lilly to acquire Ajax Therapeutics to advance outcomes for patients with myelofibrosis and polycythemia vera (PRNewswire) - "Under the terms of the agreement, Lilly will acquire Ajax and Ajax shareholders could receive up to $2.3 billion in cash, inclusive of an upfront payment and subsequent payments upon the achievement of certain clinical and regulatory milestones. The transaction is subject to customary closing conditions, including approval under the Hart-Scott-Rodino Antitrust Improvements Act of 1976.....Ajax's lead program, AJ1-11095, is a first-in-class Type II JAK2 inhibitor currently in Phase 1 clinical development, with first proof-of-concept clinical data to be presented later in 2026."

M&A • P1 data • Myelofibrosis • Polycythemia Vera

AJX-101: A Phase 1 Study of AJ1-11095 in Adults with Myelofibrosis Failed by a JAK2 Inhibitor (clinicaltrialsregister.eu) - P1 | N=20 | Not yet recruiting | Sponsor: Ajax Therapeutics Inc.

New P1 trial • Myelofibrosis

Ernest Beutler Lecture and Prize (ASH 2025) - "The ensuing years have also shown benefit of ruxolitinib on survival for MF. Subsequently, three additional JAK inhibitors — each with their own incremental benefits — have been approved (fedratinib in 2019, pacritinib in 2022, and momelotinib in 2023). A new generation of more mutant selective JAK2 inhibitors (INCB160058, AJ1-11095) is currently in early clinical trials...Radek C. Skoda will describe how the JAK2-V617F mutation drives hematopoiesis causing MPNs and recent advances in understanding of how this mutation activates the JAK2 kinase, opening new ways to find candidate drugs preferentially targeting the mutated JAK2 protein.Dr. Ruben Mesa will summarize how the single-agent JAK inhibitors significantly helped decrease the burden of MPNs and the role of current agents, the next generation of new inhibitors, and combination approaches, as well as the impact JAK inhibitors have had on non-neoplastic inflammatory disorders."

Atopic Dermatitis • Chronic Graft versus Host Disease • Dermatitis • Dermatology • Essential Thrombocythemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytosis • Vitiligo • CALR • TET2

AJ1-11095, a potent and highly selective type-II JAK2 inhibitor, shows enhanced therapeutic efficacy as compared with type-I JAK2 inhibitor ruxolitinib in models of myeloproliferative neoplasms (MPNs) (ASH 2025) - P1 | "Notably, in both models, nosignificant weight loss was observed suggesting AJ1-11095 can enhance therapeutic effect without addedtoxicity.In sum, AJ1-11095, which is currently being tested in a Phase 1 clinical trial in patients with MF refractoryto type-I JAK2i, is a potent, orally administered, highly selective type-II JAK2i that demonstrates superiorpre-clinical efficacy compared to RUX, including reductions in mutant allele burden and reticulin fibrosis,with an enhanced safety profile compared to previous type-II JAK2i. These data further demonstrate thepreclinical utility and clinical rationale for type-II JAK2i, including AJ1-11095, for the treatment of MPNs."

Clinical • Fibrosis • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • IL13 • TYK2

Ajax Therapeutics Receives Orphan Drug Designation from the U.S. FDA for AJ1-11095 for the Treatment of Myelofibrosis (GlobeNewswire)

Orphan drug • Myelofibrosis

Ajax Therapeutics Presents Preclinical Data on Differentiated Efficacy Profile of AJ1-11095, a First-in-Class Type II JAK2 Inhibitor, at the American Society of Hematology Annual Meeting (GlobeNewswire) - "In ruxolitinib-persistent JAK2 mutant cells, AJ1-11095 restored the inhibition of JAK/STAT signaling, supporting the ability to overcome type I JAK2 inhibitor mediated persistence; In a JAK2_VF knock-in competitive transplant model, AJ1-11095 demonstrated superior efficacy compared to ruxolitinib, including improvements in hematologic parameters and spleen weights, and marked reductions in mutant allele burden across peripheral blood, spleen, and bone marrow...In the hMPL^W515L myelofibrosis model, AJ1-11095 demonstrated superior efficacy compared to ruxolitinib with improvements in hematologic parameters and spleen weights....'Our Phase 1 clinical study, AJX-101, continues to enroll well and we expect to transition to the expansion phase of the study early next year.'"

Preclinical • Trial status • Myelofibrosis • Myeloproliferative Neoplasm

A Multicenter, Open-Label, Phase 1 Clinical Trial of AJ1-11095 Administered As Oral Monotherapy in Patients with Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) Who Have Been Failed By a Type I JAK2 Inhibitor (JAK2i) (ASH 2024) - P1 | "MF-directed therapy must be stopped at least 5 half-lives (5 days for hydroxyurea) before start of AJ1-11095. A Study May Proceed letter was received from the US Food and Drug Administration in May 2024. We expect to enroll the first patient in this trial September of 2024 and to activate approximately 10 sites in the US, with inclusion of sites outside the US in the dose expansion stage for a total of ~76 subjects across both stages."

Clinical • Monotherapy • P1 data • Anemia • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytosis • JAK1 • TYK2

Is Combination Therapy Here for MPN? (SOHO 2025) - "2 Outside of the potential benefit of type 2 (AJ1-11095) and JAK2 V617F-selective (INCB160058) inhibitors under phase 1 evaluation, the research community has focused efforts on developing rational JAK inhibitor-based combination therapy regimens...3 Data from prospective and retrospective studies suggest a correlation between spleen reduction and OS with ruxolitinib and pacritinib...Nevertheless, the combination of pelabresib and ruxolitinib was well tolerated, and biomarkers of disease modification — including reduction in bone marrow fibrosis, driver mutation allele frequency, and inflammatory cytokine expression levels — all favored the combination, supporting the proposed mechanism of action and published preclinical synergy...11 The phase 3 trial will aim to confirm this activity in patients who have received at least 18 weeks of ruxolitinib therapy and meet rigorously defined criteria for suboptimal response, after which these patients will be randomized to..."

Combination therapy • IO biomarker • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • CD34 • XPO1

Ajax Therapeutics and Schrödinger Expand Research Collaboration to Include Additional JAK Target (Businesswire) - "Ajax Therapeutics, Inc. and Schrödinger, Inc...announced an expansion of their exclusive research collaboration to include a new Janus kinase (JAK) target. The partnership was established in 2019 with a goal of leveraging Schrödinger’s advanced computational platform and Ajax’s structural biology insights to develop a pipeline of novel molecules, with a focus on JAK inhibitors. Ajax’s lead candidate from the collaboration, AJ1-11095, is a potential first-in-class Type II JAK2 inhibitor currently being evaluated in a Phase 1 clinical study for the treatment of myelofibrosis....Under the terms of the amended agreement, Ajax and Schrödinger will collaborate on the discovery of the development candidate, and Ajax will be responsible for clinical development and commercialization."

Licensing / partnership • Myelofibrosis

Ajax Therapeutics to Present Overview of Phase 1 Clinical Trial Evaluating AJ1‑11095, a First-in-Class Type II JAK2 inhibitor, for the Treatment of Myelofibrosis at the American Society of Hematology Annual Meeting (Businesswire) - "The poster, entitled 'A Multicenter, Open-Label, Phase 1 Clinical Trial of AJ1-11095 Administered As Oral Monotherapy in Patients with Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) Who Have Been Failed By a Type I JAK2 Inhibitor (JAK2i),' will be presented by John Mascarenhas, MD, Professor of Medicine, Icahn School of Medicine at Mt. Sinai and Director, Center of Excellence in Blood Cancers and Myeloid Disorders at Tisch Cancer Institute and principal investigator of the Phase 1 Study."

Trial status • Myelofibrosis

Ajax Therapeutics Announces First Patient Dosed in Phase 1 Clinical Trial Evaluating AJ1-11095, a First-in-Class Type II JAK2 inhibitor, for the Treatment of Myelofibrosis (Businesswire) - "The Phase 1 clinical trial is an open-label, multi-center, dose escalation and dose expansion study designed to evaluate the safety, tolerability and preliminary efficacy of AJ1-11095. The study will enroll patients with Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) who have been failed by a Type I JAK2 Inhibitor."

Trial status • Myelofibrosis

A Phase 1 Study of AJ1-11095 in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) Who Have Been Failed by a Type I JAK2 Inhibitor (JAK2i) (clinicaltrials.gov) - P1 | N=76 | Recruiting | Sponsor: Ajax Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytosis

Ajax Therapeutics Announces FDA Clearance of IND Application for AJ1-11095, a First-in-Class Type II JAK2 inhibitor, for the Treatment of Myelofibrosis (Businesswire) - "Ajax Therapeutics, Inc...announced that it has received clearance for its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) to initiate a Phase 1clinical study of AJ1‑11095, a first-in-class Type II JAK2 inhibitor, for the treatment of patients with myelofibrosis....'We look forward to the clinical development of AJ1-11095 in myelofibrosis and to initiating our Phase 1 dose escalation study, AJX-101, later this year'..."

IND • Hematological Malignancies • Myelofibrosis • Oncology

Ajax Therapeutics Raises $95 Million Series C Financing To Advance First-in-Class Type II JAK2 Inhibitor, AJ1-11095, Into The Clinic (Businesswire) - "Ajax Therapeutics...today announced the closing of an oversubscribed $95 million Series C financing. Proceeds from the financing will be used to support the clinical development of Ajax’s first-in-class Type II JAK2 inhibitor, AJ1‑11095, for the treatment of myelofibrosis, as well as advancing the company’s pipeline of treatments for MPNs....Additionally, AJ1-11095 has been shown in preclinical studies to maintain efficacy against MPN cells that become resistant to chronic Type I JAK2 inhibition."

Financing • Preclinical • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

A Phase 1 Study of AJ1-11095 in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) Who Have Been Failed by a Type I JAK2 Inhibitor (JAK2i) (clinicaltrials.gov) - P1 | N=76 | Not yet recruiting | Sponsor: Ajax Therapeutics, Inc.

New P1 trial • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytosis