apilimod dimesylate (AIT-101) / OrphAI Therap - LARVOL DELTA

Study of Safety, Tolerability, and Biological Activity of LAM-002A in C9ORF72-Associated Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2 | N=14 | Active, not recruiting | Sponsor: OrphAI Therapeutics | Phase classification: P2a ➔ P2 | Trial completion date: May 2024 ➔ Oct 2024

Phase classification • Trial completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

Apilimod dimesylate in C9orf72 amyotrophic lateral sclerosis: a randomized phase 2a clinical trial. (PubMed, Brain) - P2a | "Apilimod dimesylate met prespecified key safety and biomarker endpoints in this Phase 2a trial and demonstrated CNS penetrance and pharmacodynamic target engagement. Apilimod dimesylate was observed to have the greatest reduction in CSF poly(GP) levels observed to date in C9orf72 clinical trials."

Clinical • Journal • P2a data • Amyotrophic Lateral Sclerosis • CNS Disorders • Melanoma • Oncology • Solid Tumor • GPNMB • TARDBP

OrphAI Therapeutics receives Orphan Drug Designation for AIT-101 as a treatment for amyotrophic lateral sclerosis in the European Union (GlobeNewswire) - "OrphAI Therapeutics...announced today that it has received Orphan Drug Designation (ODD) in the European Union (EU) for the treatment of amyotrophic lateral sclerosis (ALS). AIT-101 previously received ODD from the U.S. FDA in June 2023 for the treatment of ALS."

European regulatory • Orphan drug • Amyotrophic Lateral Sclerosis

Results of a double blind,placebo-controlled clinical trial ofAIT-101 (LAM-002A) in C9ORF72ALS- A biomarker driven Phase 2aclinical trial targetingPIKfyve inhibition (ALS-MND 2023) - P2a | "Fifteen C9ORF72(þ) ALS participants with mean ageof 61. 5 (4. 78SD) years, disease duration 1."

Biomarker • Clinical • P2a data • GPNMB • NEFL • TARDBP • TFEB

AIT-101 Improves Functional Deficits in a Human TDP-43 Animal Model of ALS (ALS-MND 2023) - " 24 rNLS8 (7) mice, in which human TDP43DNLS is induced in neurons by removal of doxycycline, were maintained on a doxycycline diet, and at 10 weeks-of-age, 12 mice per group were treated with 60mg/kg AIT-101 or vehicle b.i.d. AIT-101 treatment of rNLS8 mice led to significant improvements in body weight (p < 0.0001 two-way ANOVA interaction term), clasping (p = 0.001), hindlimb paralysis (p = 0.015) and grill agility (p = 0.001) at Week 3, and a composite score (clasping, hindlimb paralysis, grill agility, tremor and overall wellbeing) after Day 6 (p 0.048) and after Weeks 2 and 3 (p 0.01). There were also significant decreases in CSF (p < 0.00001) and plasma (p = 0.03) levels of neurofilament light (NfL). Quantitative IHC staining for hTDP43 and GFAP, a marker of neuroinflammation, showed significant decreases with AIT-101 in several areas of the cortex and corticospinal tract."

Preclinical • Inflammation • Movement Disorders • CLSPN, • CSF NfL • FAP • GFAP • TARDBP • TFEB

Study of Safety, Tolerability, and Biological Activity of LAM-002A in C9ORF72-Associated Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2a | N=14 | Active, not recruiting | Sponsor: AI Therapeutics, Inc. | Trial completion date: Sep 2023 ➔ May 2024

Trial completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

OrphAI Therapeutics Announces Oral Presentation and Posters at the 22nd Annual NEALS Conference (GlobeNewswire) - "OrphAI Therapeutics Inc...announced today data presentations at the 22nd Annual NEALS (Northeast ALS Consortium) meeting being held October 4 - 6, 2023 in Clearwater Florida."

P2a data • Preclinical • Amyotrophic Lateral Sclerosis

AI Therapeutics Announces Positive Results from Phase 2a Biomarker-driven Trial of AIT-101 in Patients with C9ORF72 Amyotrophic Lateral Sclerosis (ALS) (GlobeNewswire) - P2a| N=14 | NCT05163886 | Sponsor: Jiangsu HengRui Medicine Co., Ltd | "AI Therapeutics...announced today positive results from a Phase 2a clinical trial of AIT-101 (LAM-002A) in patients with C9ORF72 amyotrophic lateral sclerosis (ALS). In the study, participants taking AIT-101 demonstrated increased expression of the target engagement biomarker (sGPNMB) and a 73% reduction in the toxic protein aggregate (poly(GP)) over 12 weeks. The study also met its primary endpoints of safety and tolerability, and confirmation of delivery of drug and three active metabolites into the brain....Detailed results from the Phase 2a trial and the TDP-43 animal model will be submitted for peer-reviewed publication and presentation at a future medical congress."

Biomarker • P2a data • Amyotrophic Lateral Sclerosis • CNS Disorders

A Study of LAM-002A for the Prevention of Progression of COVID-19 (clinicaltrials.gov) - P2 | N=142 | Completed | Sponsor: AI Therapeutics, Inc. | Unknown status ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease

Study of Safety, Tolerability, and Biological Activity of LAM-002A in C9ORF72-Associated Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2a | N=14 | Active, not recruiting | Sponsor: AI Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2022 ➔ Sep 2023

Enrollment closed • Trial completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

An Open-Label, Expanded Access Protocol of LAM-002A in C9ORF72-Associated Frontotemporal Dementia (FTD) (clinicaltrials.gov) - P=N/A | N=N/A | No Longer Available | Sponsor: AI Therapeutics, Inc.

New trial • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Immunology

A Phase I Dose Escalation Study of the Safety and Pharmacokinetics of LAM-002A In Patients With Non-Hodgkin's Lymphoma (LAM-002A/NHL) (clinicaltrials.gov) - P1 | N=62 | Active, not recruiting | Sponsor: AI Therapeutics, Inc. | Completed ➔ Active, not recruiting | Trial completion date: Aug 2020 ➔ Mar 2023

Enrollment closed • Trial completion date • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Study of Safety, Tolerability, and Biological Activity of LAM-002A in C9ORF72-Associated Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2a; N=12; Recruiting; Sponsor: AI Therapeutics, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Amyotrophic Lateral Sclerosis • CNS Disorders

Study of Safety, Tolerability, and Biological Activity of LAM-002A in C9ORF72-Associated Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2a; N=12; Not yet recruiting; Sponsor: AI Therapeutics, Inc.

Clinical • New P2a trial • Amyotrophic Lateral Sclerosis • CNS Disorders

A Phase I Dose Escalation Study of the Safety and Pharmacokinetics of LAM-002A In Patients With Non-Hodgkin's Lymphoma (LAM-002A/NHL) (clinicaltrials.gov) - P1; N=62; Completed; Sponsor: AI Therapeutics, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

[VIRTUAL] Results of a completed phase I study of LAM-002 (apilimod dimesylate), a first-in-class phosphatidylinositol-3-phosphate 5 kinase (PIKfyve) inhibitor, administered as monotherapy or with rituximab or atezolizumab to patients with previously treated follicular lymphoma or other B-cell cancers. (ASCO 2020) - P1 | "Background: LAM-002 is a selective inhibitor of PIKfyve that disrupts lysosomal homeostasis, inducing cytotoxicity in B-cell lymphoma models as monotherapy or with anti-CD20 or anti-PDL1 antibodies (Gayle et al., Blood 2017;129(13):1768). LAM-002, the first clinical PIKfyve inhibitor, is safe alone or with full-dose anti-CD20 or anti-PD-L1 inhibition. LAM-002 does not cause the myelosuppressive or immune adverse events associated with lenalidomide or PI3K inhibitors. Promising efficacy supports registration-directed Phase 2/3 testing of LAM-002 monotherapy and combination therapy for patients with previously treated follicular lymphoma."

Clinical • Monotherapy • P1 data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

The PIKfyve Inhibitor Apilimod: A Double-Edged Sword against COVID-19. (PubMed, Cells) - "However, although apilimod might prevent viral invasion by inhibiting host cell proteases, the same proteases are critical for antigen presentation leading to T cell activation and there is good evidence from both in vitro studies and the clinic that apilimod blocks antiviral immune responses. We therefore warn that the immunosuppression observed in many COVID-19 patients might be aggravated by apilimod."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study of LAM-002A for the Prevention of Progression of COVID-19 (clinicaltrials.gov) - P2; N=142; Recruiting; Sponsor: AI Therapeutics, Inc.; Trial primary completion date: Dec 2020 ➔ Mar 2021

Clinical • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

AI Therapeutics Announces Start of Phase II Trial of LAM-002A (apilimod dimesylate) for Treatment of COVID-19 Patients (Businesswire) - "AI Therapeutics announced the start of Phase II clinical trial for the treatment of newly diagnosed COVID-19 patients in collaboration with Yale University....The randomized, double-blind, placebo-controlled study...will enroll up to 142 outpatients to evaluate the safety, tolerability, and efficacy of LAM-002A in reducing viral load in subjects with a confirmed COVID-19. Additional measures of clinical efficacy will be evaluated, including death, hospitalization, and oxygen saturation."

Trial status • Infectious Disease • Novel Coronavirus Disease

Coronavirus and cancer hijack the same parts in human cells to spread – and our team identified existing cancer drugs that could fight COVID-19 (The Conversation) - "For years, researchers have suspected that kinases...could be targeted to fight infections....We identified a few already existing cancer drugs which alter the function of the kinases....There are 87 existing drugs that change the kinase-controlled pathways used by the coronavirus....Our collaborators in New York and Paris tested the effect of 68 of those drugs on cells infected with SARS-CoV-2. Several of these were effective in killing the virus in cells. A few that we are especially excited about – silmitasertib, gilteritinib, ralimetinib, apilimod and dinaciclib – are either approved for treatment, in clinical testing or under preclinical development for various diseases."

Clinical • Cytokine storm • Preclinical • Infectious Disease • Novel Coronavirus Disease

A Study of LAM-002A for the Prevention of Progression of COVID-19 (clinicaltrials.gov) - P2; N=142; Recruiting; Sponsor: AI Therapeutics, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Infectious Disease • Novel Coronavirus Disease • PCR

A Study of LAM-002A for the Prevention of Progression of COVID-19 (clinicaltrials.gov) - P2; N=142; Not yet recruiting; Sponsor: AI Therapeutics, Inc.

Clinical • New P2 trial • Infectious Disease • Novel Coronavirus Disease • PCR

AI-based platform suggests cancer candidate LAM-002 as possible ALS therapy, AI therapeutics says (ALS News Today) - “AI Therapeutics‘ lymphoma candidate LAM-002 was identified by the company’s artificial intelligence-based platform — called Guardian Angel — as a possible treatment for amyotrophic lateral sclerosis”

Clinical

AI Therapeutics announces that a common LAM-002 mechanism in cancer and neurodegenerative diseases shows antitumor activity in the clinic and hope for ALS (Businesswire) - "The company has made significant recent progress with its four clinical assets and proprietary Guardian Angel™ algorithm....We look forward to bringing the most advanced PIKfyve inhibitor into clinical development for patients suffering from ALS. We are pleased that our Guardian Angel^TM platform made the connection of LAM-002 to ALS and that the finding was validated in our laboratories and with our collaborators, as well as in independent research published in Nature Medicine."

Clinical

A Phase I Dose Escalation Study of the Safety and Pharmacokinetics of LAM-002A In Patients With Non-Hodgkin's Lymphoma (LAM-002A/NHL) (clinicaltrials.gov) - P1; N=62; Active, not recruiting; Sponsor: AI Therapeutics, Inc (formerly known as LAM Therapeutics, Inc.); Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed