Start-up Calmodulis Therapeutics: Next-generation Therapies for Lipid-dependent Cancers

Technology Overview

Calmodulis Therapeutics is a proposed Monash University spin-out to develop novel, highly selective, first-in-class CAMKK2 inhibitors for lipid-dependent cancers. The lead program is a monotherapy and combination therapy with standard of care (SOC) for patients with advanced prostate cancer (mCRPC), with potential label expansion to earlier disease stages.

Support for this target and approach is compelling:

• CAMKK2 is the core component of a cell signaling pathway activated by Ca 2+ -calmodulin and long-chain, saturated fatty-acid metabolites
• CAMKK2 expression tracks with Gleason grade, recurrence, and metastasis in patients, and is associated with poor prognosis and decreased survival
• Inhibition of CAMKK2:
  • breaks the “vicious cycle” loop with the androgen receptor and blocks prostate cancer growth, progression, and metastasis
  • protects against diabetes, metabolic syndrome, and bone loss - major side effects associated with SOC androgen deprivation therapy
• Product Type: Orally administered small molecule.
• Indication: Prostate Cancer, Hepatocellular Carcinoma, and other lipid-dependent cancers and diseases.
• Target/Mechanism of Action:
  • Novel MoA: Targeting lipid metabolism for the treatment of cancers.
  • Novel first-in-class Ca2+-calmodulin dependent protein kinase kinase-2 (CAMKK2) inhibitor for the treatment of lipid-dependent cancers.

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Further Details:

Lin et al, Oncogene, 2021, 40, p1690; Eduful et al, J Med Chem, 2021, 64, p10849.

Stage of Development

Lead Series with favorable pharmacokinetic (PK) parameters.

Future: Short-term milestones include detailed characterisation of lead series pharmacology and PK, organoid and in vivo PoC studies, and CMC program for lead drug candidate selection.

Benefits

Calmodulis Therapeutics CAMKK2 inhibitors are:

• Highly potent: picomolar to low nanomolar affinity.
• Exquisitely selective: Inhibits < 1% of other kinases (at 1 μM).
• Orally bioavailable: Optimal plasma exposure and half-lives (Cmax: 53 μM, Tmax 1h, t1/2: 9.4 hr).

Applications

Indications: Prostate Cancer, Hepatocellular Carcinoma, and other lipid-dependent cancers and diseases.

Opportunity

Monash University is seeking early-stage investment or partnering with industry to rapidly progress this promising technology.