Open Label Extension Study of PREOS

Effects of ALX1-11 on bone mineral density (BMD) have been documented in a dose-finding
Phase II clinical trial in osteoporotic postmenopausal women, supplemented with calcium and
Vitamin D3 but without any other treatment for osteoporosis. The anabolic effects of ALX1-11
in the lumbar vertebrae were statistically significant after the 12-month treatment period
and more pronounced than any approved therapy. Additionally, animal studies have shown that
the new bone formed by treatment with ALX1 11 is of good quality both histologically and
biomechanically.

The primary objective of this OLES is to evaluate the safety of continued dosing with
ALX1-11, up to a maximum of 24 months, in postmenopausal osteoporotic women who participated
in Protocol ALX1-11-93001. A secondary objective is to assess the change in vertebral BMD
and compare the changes observed in patients who received ALX1-11 or placebo in Protocol
ALX1-11-93001.

Patients will receive 100 µg/day of ALX1-11 daily via subcutaneous injection in this study.
Patients should continue the study drug dosing frequency they were following at the end of
Protocol ALX1-11-93001.

To enhance their safety, all patients will continue to take their daily supplements of 700
mg calcium and 400 IU Vitamin D3 prior to and during this OLES. Patients whose calcium
supplement was discontinued during Protocol ALX1-11-93001 should maintain that
discontinuation during this OLES. However upon completion of ALX1-11 dosing in the OLES,
oral calcium supplement at a dose of 700 mg each morning should be restarted and maintained
for the remainder of the OLES. Additional supplemental calcium and/or Vitamin D3 will not be
permitted. A daily multivitamin supplement may be taken during the study. However, the
multivitamin must contain no more than 200 mg/day calcium and 400 IU/day Vitamin D3.
Patients will be monitored for the development of hypercalcemia and/or hypercalciuria and
managed as described in Appendices 4 and 5.

There will be a stopping rule in this OLES. Any patient who reaches a BMD T score of -0.5 or
above, at the site or sites (vertebral, total hip, or femoral neck) that were used in the
qualification of the patient for Protocol ALX1 11-93001, will stop ALX1-11 treatment. The
patient must continue on calcium and Vitamin D3 and be followed for the remainder of this
18-month OLES. At the time of discontinuation, the patient must complete the Month 18
evaluations (Appendix 1A or 1B).

The Clinical Advisory Board (CAB) used in Protocol ALX1-11-93001 will be involved in
reviewing any patient issues that arise in this OLES. This group will provide not only
continuity of care for all the patients, but also enhanced and consistent safety monitoring
for patients participating in the OLES.

Inclusion Criteria:

- Women who completed 18 months of treatment in Protocol ALX1-11-93001; or

- Women prematurely discontinued from Protocol ALX1-11-93001 who want to participate in
OLES for the events listed below must have their clinical course reviewed and
approved by the CAB for enrollment into the OLES:

- Clinical or incident lumbar vertebral fractures as assessed by the central
imaging organization

- Clinical or incident hip fracture

- Confirmed bone loss at A/P lumbar vertebra or total hip or femoral neck as
assessed by the central imaging organization

- Body weight below 40 kg

- Development of an exclusion criterion in Protocol ALX1-11-93001

- It must be accepted by patients whose clinical courses are reviewed by the CAB that
participation in OLES may require additional tests at baseline and/or during the
study to ensure their utmost safety.

- Women with the ability to self-administer a daily injection or have a designee who
will give the injections;

- Women who are capable of understanding and giving written, voluntary informed consent
before the start of open-label dosing with ALX1-11.

Exclusion Criteria:

A. History or Concurrent Illness:

Disorders of Immunity Endocrine system Gastrointestinal system Kidney and collecting
system Liver, biliary tract and pancreatic systems Musculoskeletal system

- Patients with chronic, active joint disease requiring more than one intra-articular
injection every 6 months Neoplasia

- Patients who have had squamous or basal cell carcinoma of the skin may enter this
study if:

1. The lesion(s) were fully resected with clear margins described in a written
report by a pathologist, and

2. The patient has had no recurrence of lesions for at least one year from the time
of the original resection.

Nervous system Vascular, respiratory and cardiac system *Significant diseases or
disorders are determined by history, physical exam or laboratory tests and
judged by the Principal Investigator to be significant.

B. Concurrent Medication:

Patients may not use any of the following therapies while they are enrolled in
this OLES without permission from the Sponsor and the PMO:

- Tetracycline antibiotics for four weeks prior to bone biopsy

- Any PTH analogs [e.g., rhPTH(1-84), PTH(1-34), PTHrP and analogs]

- Fluoride

- Strontium

- Phenytoin for seizure control

- Any investigational drug other than ALX1-11

- Anabolic steroids or androgens

- Active Vitamin D3 metabolites and analogs, e.g., calcitriol

- Systemic corticosteroids, more than 5 mg/day prednisone or a systemic
corticosteroid formulation equivalent to 5 mg/day prednisone

1. A patient who has been enrolled into the OLES and needs to receive an acute bolus
of steroids (oral or injectable) for a self-limited illness may continue treatment in
the study if the following requirements are met:

1. Exposure to steroids will be limited to no more than 30 consecutive days

2. The maximal dose of steroid (prednisone equivalent) must be limited to no more
than 225 mg (7.5 mg each day for 30 days)

3. The illness is acute in nature and is not expected to recur during the remaining
period of the study

- Bisphosphonates, including investigational bisphosphonates

- Calcitonin

- Estrogen replacement therapy by oral, transdermal or intramuscular
administration

- SERM drugs, e.g., tamoxifen, raloxifene, Evista

- Vaginal application of estrogen-containing creams unless the dose is:

1. conjugated estrogen or estradiol: maximum of 0.5 g twice each week
(total of 1.0 g weekly)

2. Estrace (Ogen): maximum of 1.0 g twice each week (total of 2.0 g
weekly)

- Daily inhaled corticosteroid unless dose is equivalent to <1200 µg/day of
beclomethasone

- Cytostatics, e.g., azathioprine, recombinant human tumor necrosis fusion
(Fc) protein, monoclonal antibody against tumor necrosis factor (e.g.,
remicade [infliximab]

- Methotrexate

1. The antimetabolite, methotrexate, which interferes with DNA synthesis,
repair and cellular replication should not be used by patients
participating in this OLES.

- In general, immunomodulatory agents with antiproliferative activity are not
permitted as a concomitant medication in this OLES.

- Intra-articular injections

1. Patients may receive a maximum of one intra-articular injection (ONE
JOINT ONLY) every 6 months while participating in this OLES. The joint that
is injected may be a different joint every 6 months. The dose of
corticosteroid injected should not exceed the anti-inflammatory equivalent
dose of Prednisone 40 mg suspension. The dose and volume should be adjusted
downward as appropriate to the size of the joint.

- Provera is an acceptable concomitant medication when used according to the
label instructions

Patients may be enrolled in this OLES if they have been stabilized on the
following therapy for the specified amount of time:

- Thyroid Hormone (<0.1 mg/day thyroxine) therapy for at least 6 months If
taking > 0.1 mg/day but < 0.2 mg/day, must have serum TSH level 1. >
0.1mU/L. Patients will be excluded if they are taking doses of > 0.2
mg/day.

2. However, if a patient has had a minimal change in L-thyroxine dose of <
0.025 mg/day within 6 months of the baseline visit, and has been on this
new dose for at least 2 months, the patient may be enrolled in this study.
The patient's history with L-thyroxine must be clearly documented in the
source documents.

3. If a patient requires an increase in their thyroid replacement dose, as
recommended by a physician who is caring for the patient, after enrollment
in this OLES, the patient must have a TSH and T4 level within 3 months of
the dose change to ensure the patient does not become hyperthyroid

- Stable dosage of thiazide for at least 3 consecutive months

C. Laboratory Values and Physical Examination Findings:

- Serum calcium greater than 10.7 mg/dL (2.66 mmol/L) at baseline will be
managed as outlined in Appendix 4

- Urinary calcium to creatinine ratio greater than or equal to 1 at baseline
will be managed as outlined in Appendix 5

- Elevated total serum alkaline phosphates (> 400 U/L) at baseline will be
managed as outlined in Appendix 6 except as noted for Latin and South
American countries.

- Any other clinically significant abnormal value as judged by the
investigator

D. Substance Abuse:

Alcohol and/or drug abuse

E. Compliance:

Suspected or confirmed poor compliance in completing clinical trial evaluations
and/or clinical trial required questionnaires