Phase 3 Study to Evaluate the Efficacy & Safety of Self-Administered Injections of BMN165 by Adults With PKU

165-302 is a Phase 3, 4 Part, Randomized, Double-Blind, Placebo-Controlled, Discontinuation
Study to Evaluate the Efficacy and Safety of Self Administered Subcutaneous Injections of BMN
165 by Adults With PKU.

This study is open only to adults who have been exposed to BMN165 in a previous study.

Study BMN 165-302 is a four-part, Phase 3 study.

- PART 1: Open-label period

- PART 2: A Randomized, double-blind, placebo-controlled period of 8 weeks

- PART 3: PK (plasma BMN 165) and PD (plasma Phe) assessment.

- Part 4: A long-term, open-label extension study.

INCLUSION CRITERIA

Individuals eligible to participate in this study must meet all of the following criteria:

- Have completed a prior BMN 165 study (PAL-003 or 165-301) prior to screening

- Have had a stable BMN 165 dose regimen for at least 14 days prior to screening

- Are at least 18 y/o and no older than 70 y/o at screening

- Subjects who are < 18 y/o and are already enrolled into Study 165-301 under
Amendment #1 (10JAN2014) may enroll into this study

- Has identified a person who is ≥ 18 y/o who has the neurocognitive and linguistic
capacities to comprehend and complete the POMS-Observer rated scale

- Has identified a competent person(s) ≥ 18 y/o who can observe the subject during study
drug administration at certain points in the study

- A home healthcare nurse may perform the study drug observations

- Are willing and able to provide written, signed informed consent after the nature of
the study has been explained and prior to any research-related procedures; for minors,
parent or guardian provides written consent and assent may be requested

- Are willing and able to comply with all study procedures

- For females of childbearing potential, a negative pregnancy test at screening and
willing to have additional pregnancy tests during the study

- If sexually active, willing to use two acceptable methods of contraception during and
for 4 weeks after the study

- Males post vasectomy for 2 years with no known pregnancies do not need to use any
other forms of contraception during the study.

- Females who have been in menopause for at least 2 years, have had a tubal
ligation at least 1 year prior to screening, or have had a total hysterectomy do
not need to use any other forms of contraception during the study.

- Have received documented approval from a study dietitian confirming that the subject
is capable of maintaining their diet

- Have neurocognitive and linguistic capacities to comprehend and answer investigator's
prompts for the ADHD-RS Investigator rated instrument and to complete the POMS-Subject
rated scale

- If applicable, maintained stable dose of medication for ADHD, depression, anxiety, or
other psychiatric disorder ≥8 weeks prior to enrollment and willing to maintain stable
dose throughout study unless a change is medically indicated

- General good health, as evidenced by physical examination, clinical laboratory
evaluations, and ECG tests at screening

Exclusion Criteria

Individuals who meet any of the following exclusion criteria will not be eligible to
participate in the study:

- Use of any investigational product (except BMN 165) or investigational medical device
within 30 days prior to screening or requirement for any investigational agent prior
to completion of all scheduled study assessments

- Use of any medication (except BMN 165) intended to treat PKU, including the use of
large neutral amino acids, within 2 days prior to the administration of study drug

- Have known hypersensitivity to Dextran® or components of Dextran

- Use or planned use of any injectable drugs containing PEG (except for BMN 165),
including medroxyprogesterone injection, within 3 months prior to screening and during
study participation

- Current use of levodopa

- A positive test for HIV antibody, hepatitis B surface antigen, or hepatitis C antibody

- A history of organ transplantation or taking chronic immunosuppressive therapy

- A history of substance abuse in the past 12 months or current alcohol or drug abuse

- Current participation in the Kuvan registry study (PKUDOS). Patients may discontinue
the PKUDOS registry trial to allow enrollment in this study

- Pregnant or breastfeeding at screening or planning to become pregnant (self or
partner) or breastfeed at any time during the study

- Concurrent disease or condition that would interfere with study participation or
safety.

- Major surgery planned during the study period

- Any condition that in the view of the investigator, places the subject at high risk of
poor treatment compliance or terminating early from the study

- ALT concentration at least 2x the upper limit of normal

- Creatinine at least 1.5x the upper limit of normal