AI-based Platform Suggests Cancer Candidate LAM-002 as Possible ALS Therapy, AI Therapeutics Says

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 (ALS).

Researchers from AI have already tested and confirmed LAM-002’s therapeutic potential in an ALS context.

Now, an independent study, “Haploinsufficiency Leads to Neurodegeneration in C9ORF72 ALS/FTD Human Induced Motor Neurons,” was published in Nature Medicine.

LAM-002 (apilimod) is an inhibitor of the PIKfyve kinase that works by clearing toxic protein aggregates, or clumps, within lysosomes — cell compartments in which unwanted molecules are broken down or digested. Abnormal lysosomal function is commonly observed in neurodegenerative diseases like Parkinson’s and ALS.

More specifically, LAM-002 activates the transcription factor EB, which in turn stimulates the production of new lysosomes.

AI Therapeutics’ deep learning platform, Guardian Angel, had identified LAM-002 — an investigational therapy for B-cell non-Hodgkin lymphoma — as a possible treatment for ALS. The artificial intelligence technology synthesizes public and proprietary data on medications and diseases and finds new indications for the company’s library of new chemical products.

Importantly, scientists at AI Therapeutics and other independent studies have already validated the platform’s “suggestion” in the laboratory. The compound was seen to ameliorate ALS-related disease processes in motor neurons.

For the new study, researchers used human motor neurons carrying a mutation in the C9ORF72 gene — one of the most commonly mutated genes in ALS. The C9ORF72 protein is needed for the production of lysosomes in motor neurons, and mutations in this protein lead to the build-up of toxic proteins that are inadequately cleared in lysosomes.

Inhibiting the PIKfyve kinase, however, appears to increase lysosome activity, “and may compensate for reduced C9ORF72 activity,” the researchers said.

AI Therapeutics is preparing to move LAM-002 into a Phase 2 clinical trial for people with ALS.

“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 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,” Murat Gunel, MD, professor of neurosurgery and genetics at Yale University and a member of AI Therapeutics’ Scientific Advisory Board, said in a press release.

The candidate also is being tested as a treatment for follicular lymphoma, a kind of B-cell non-Hodgkin’s lymphoma. This type of cancer can arise from overactive or high levels of kinases. By targeting the activity of PIKfyve, LAM-002 is able to kill these cancer cells without harming normal cells.

Following a Phase 1 study in follicular lymphoma, LAM-002 was shown to be safe and well-tolerated, and to have anti-tumor activity in patients who had failed multiple prior lines of therapy. Studies indicate LAM-002 is effective as a single agent, but also when combined with rituximab or Tecentriq (atezolizumab), both cancer medications.

“LAM-002 represents a novel targeted approach to treat patients with follicular lymphoma. Our patients have shown durable objective responses while on LAM-002 therapy without the adverse effects often associated with other drugs,” said Sarah Rutherford, MD, assistant professor at Weill Cornell Medicine.

In a recent Type C meeting with the U.S. Food and Drug Administration (FDA), AI Therapeutics defined a design for a pivotal trial for LAM-002 use in people with previously treated follicular lymphoma. This new study holds the potential to support an application requesting the therapy’s approval in the U.S.

The FDA has already granted fast track and orphan drug status to LAM-002 for the treatment of follicular lymphoma.

Investigators plan to present LAM-002’s safety and clinical data at this year’s American Society of Clinical Oncology (ASCO) conference, to be held May 29 through June 2 in Chicago.