Rhodase™ - Rr Platform Technology Component

Rhodase is potentially a safer and more effective novel treatment for Acute Lymphoblastic Leukemia. Rhodase is L-asparaginase from Gram-positive R. rhodochrous. The R. rhodochrous bacterium is ubiquitous in soils. R. rhodochrous does not contribute to any pathogenesis and is capable of using a wide range of organic compounds as sole sources of carbon and energy to support growth.

Acute lymphoblastic leukemia (ALL)

Acute lymphoblastic leukemia (ALL) – is the most prevalent form of childhood cancer. ALL accounts for 80% of leukemia cases diagnosed in children under age 5. Nearly 88% of children who complete the treatment with  asparaginase experience 10 years leukemia-free. There is a 94% overall survival at 10 years. Patients who complete all doses of Asparaginase treatments have better outcomes and lower rates of recurrence than those who do not.

The current standard treatment for ALL in juvenile many adult protocols is Asparaginase therapy (with or without chemotherapy). Acute lymphoblastic leukemia cells lack the ability to synthesize the amino acid L- asparagine. When a patient has ALL, leukemia cells cannot make L- asparagine and are forced to obtain it from the host bloodstream. Depletion of asparagine and the inability to synthesize protein leads to cell death.

The Crowpierce Rhodase™ technology addresses current treatment issues.

The Crowpierce Rhodase™ technology addresses current treatment issues.

  • Rhodase uses L-asparaginase derived from R. rhodochrous which has more robust asparaginase activity than Gram-negative bacteria.


  • R. rhodochrous is a Gram-positive bacterial source so there are no lipopolysaccharides present to trigger allergic reactions or resistance.


  • R. rhodochrous produces high yields of L-asparaginase used to make Rhodase


  • Based on the present treatment regimen, our smallest reactor can make enough fresh asparaginase to treat 1000 patients.

Since the discovery of the utility of asparaginase and the commercialization of the E. coli and Erwinia enzymes, the literature is filled with reports of enzyme sources in a wide range of microorganisms. Most of these studies are based on only small volumes of culture and the feasibility of scale up to commercial levels is challenging.  Our technology has demonstrated that scale up to over-produce quantities of very active stable enzyme preparations is reasonable.

Large market looking for better solution

  • Assuming at least $75-250,000 for course of treatment and ~3,000 new cases diagnosed each year, market potential for new juvenile cases in US is at least $225M
  • Market could double if one includes patients discontinuing treatment with existing forms of L-asparaginase due to resistance or toxicity or possible adult ALL 
  • All new cases of ALL in US represent a market opportunity reaching $500M
  • 80,000 people are living with ALL in US
  • There is a shortage of asparaginase available for treatment

Rhodase – Product Profile

  • High levels of asparaginase activity – Facilitates recovery and purification
  • Endotoxin-free
  • Novel sequence – Ensures no reactivity with pre-formed, anti-E coli/Erwinia asparaginase antibodies
  • Product contains glutaminase which addresses problem of asparaginase resistance
  • Better stability
  • Longer half-life

Challenges with Current L-asparaginase Treatment

Challenges with Current L-asparaginase Treatment

  • Most patients are at risk for severe and sometimes fatal allergic reactions
  • Standard practice involves topical testing with L-asparaginase on a patient’s skin prior to dosing
  • Many physicians consider L-asparaginase so immunogenic that treatment often restricted to facilities that can treat anaphylaxis
  • Hypersensitivity reactions have been observed in up to 70% of patients treated with non-pegylated asparaginase
  • Risk of reaction increases with number of doses
  • One-third of patients experience reaction by fourth dose

Current L-asparaginase treatments, whether native or modified by pegylation, come from Gram-negative bacteria such as E. coli and Erwinia chrysanthemi. L-asparaginase from Gram-negative bacteria contain immune-stimulating factors. Gram-negative bacteria have outer cell walls coated with lipopolysaccharides with endotoxins that trigger a powerful immune response. Even very low concentrations of lipopolysaccharides are enough to stimulate the body’s innate and adaptive immune system. Gram-positive cells do not have lipopolysaccharides. The current clinical protocol is to switch patients to a different type of L-asparaginase during an allergic reaction.

When L-asparaginase triggers allergic reactions the dosing must be reduced or discontinued. Common L-asparaginase toxicities are: Serum sickness, Cerebral dysfunction, Pancreatitis, Elevated hepatic enzymes, Decreased protein synthesis, Thrombosis, Hypoalbuminemia, Hyperglycemia, Hypersensitivity, Anaphylaxis.

Patients treated with L-asparaginase that do not develop serious allergic reactions often develop rapid drug resistance as the body produces neutralizing antibodies to foreign protein. The specific mode of resistance has not been fully characterized. The phenomenon is known as “silent inactivation.”