BioFe, Medical Food for the Dietary Management of Iron Deficiency

Iron deficiency is the most common, widespread, and costly nutritional disorder worldwide
with the World Health Organization (WHO) stating that up to 2 billion people are iron
deficient. There is a serious and widespread misconception that oral iron supplements are
safe and effective at alleviating iron deficiency. In a recent Cochrane review of 67 clinical
trials, women taking oral iron supplements had a mere 38% decreased risk of iron deficiency
compared to placebo. On the contrary, these subjects had a 114% increased risk of side
effects, the vast majority of which were associated with gastrointestinal (GI) disturbance.

In infants and children, iron deficiency impedes mental, motor, and auditory neuronal
development leading to serious lifelong cognitive and physical deficiencies. In adults, iron
deficiency, and associated iron deficiency anemia, cause extreme fatigue, decreased immune
system function and increased susceptibility to infectious disease, reduced work capacity,
dizziness, headaches, hair loss, and generalized reduced quality of life. Iron deficiency is
also linked to Restless Leg Syndrome (RLS), adult hearing deficits, reduced strength,
coordination, and endurance, anxiety, increased heart failure morbidity, decreased
intellectual performance, and erectile dysfunction among many others conditions.

Most iron deficient people are not effectively treated by, or are intolerant to, oral iron
supplements. Intravenous iron repletion drugs effective, but are also costly and onerous to
deliver leading to both patient and payor dissatisfaction.

BioFe, Medical Food for Iron Deficiency is nutritional/Baker's yeast (Saccharomyces
cerevisiae), expressing the Ferritin protein. Ferritin is an indispensable iron storage,
transport and absorption protein normally produced at low levels by almost all living
organisms. An illustrative example of the biology of the Ferritin/Iron complex is its
presence in human breast milk, providing infants the natural biological iron required for
rapid learning and development, without gastrointestinal upset. BioFe provides high level
expression of Ferritin that is naturally complexed with iron during culture, is pasteurized,
and dried.

Inclusion Criteria:

- Moderate iron deficiency defined as transferrin saturation (TSAT) <20% and serum
ferritin <50 ng/mL.

Exclusion Criteria:

- Female subjects who are pregnant, plan to become pregnant, or not willing to use an
acceptable form of contraception (tubal ligation or otherwise be incapable of
pregnancy, hormonal contraceptives, spermicide plus barrier, or intrauterine device).

- Female subjects who are breastfeeding or plan to breastfeed after enrolling in the
study.

- Hemochromatosis or other iron storage disorders.

- Hemoglobin below 8 g/dL.

- Previous gastric bypass, sleeve gastrectomy, or gastric band surgery.

- Currently on iron supplements and/or multivitamins containing iron (subjects may be
pre-screened four weeks prior to the screening visit in order to stop/washout or
switch to vitamins not containing iron).

- Currently on monoamine oxidase inhibitors (MAOIs) or Demerol.

- Current diagnosis of asthma and is actively using anti-asthmatic therapy.

- Smoking within two weeks of screening, current smoking, or anticipated smoking after
enrolling in the study.

- Active malignancy within one year of screening.

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than two
times the upper limit of normal.

- Known positive Hepatitis B, Hepatitis C, or HIV-1/HIV-2.

- Unregulated hypertension, chronic kidney disease, irritable bowel syndrome, anemia of
chronic diseases, chronic autoimmune inflammatory condition.

- Significant cardiovascular disease or congestive heart failure.

- Known allergy to yeast or any other component of BioFe.

- Received an investigational drug within 30 days of screening.

- Any laboratory abnormality, medical condition or psychiatric disorder, which in the
opinion of the clinical principal investigator or Sponsor, may result in the subject
being unable to comply with study requirements.