Study of Long-term Safety, Efficacy Tolerability of BYM338 in Patients With Sporadic Inclusion Body Myositis

This is a non-confirmatory, multicenter, open-label, non-randomized trial which will extend
active treatment to those patients that participated in the preceding proof-of-concept study
(CBYM338X2205) in order to collect long-term safety and tolerability data. Up to 14 patients
with sIBM will be invited to enroll into the study to receive BYM338 open-label for a period
of approximately 3 years or until BYM338 is commercially available, whichever comes first.
The study consists of a maximum 28-day screening period, a 5-day baseline period, and a
treatment period consisting of the site visits at 4-week intervals for treatment
administration, safety and pharmacokinetic follow-up. All patients will be administered a
medium level i.v. BYM338 dose regardless of their treatment allocation in the prior study.

Inclusion Criteria:

- Written informed consent must be obtained before any assessment is performed.

- Patients who participated in the CBYM338X2205 study. A patient is defined as
participating in the study if they were enrolled and received study medication.

- Able to communicate well with the investigator, to understand and comply with the
requirements of the study.

Exclusion Criteria:

- Patients for whom the treating physician considers it inappropriate for continuation
into the study, including consideration of physical and laboratory assessment of the
patient at screening.

- Patients who were non-compliant or demonstrated a serious protocol deviation in the
previous study.

- Use of other investigational drugs at the time of enrollment, within 30 days or 5
half-lives of enrollment, or until the expected PD effect has returned to baseline,
whichever is longer; or longer if required by local regulations.

- History of hypersensitivity to any of the study drugs or to drugs of similar chemical
classes

- Swallowing difficulty or other reason that precludes adequate intake of energy and
protein, defined as at least 20 kcal/kg/day and 0.6 g protein/kg/day as determined by
the investigators assessment.

- On the Columbia-Suicide Severity Rating Scale, a score of 4 or 5 on the Suicidal
Ideation item or any "yes" on the Suicidal Behavior item that is related to suicidal
behavior occurring during the last 2 years.

- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive hCG laboratory test.

- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, must use highly effective contraception during the study and for 5
half-lives (14 weeks) after stopping treatment. Highly effective contraception is
defined as either:

1. Total abstinence: When this is in line with the preferred and usual lifestyle of
the subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception].

2. Sterilization: have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks before taking study treatment.
In case of oophorectomy alone, only when the reproductive status of the woman has
been confirmed by follow up hormone level assessment.

3. Male partner sterilization (with the appropriate post-vasectomy documentation of
the absence of sperm in the ejaculate). [For female study subjects, the
vasectomized male partner should be the sole partner for that patient].

4. Use of a combination of any two of the following (a+b or a+c or b+c):

1. Use of oral, injected or implanted hormonal methods of contraception.

2. Placement of an intrauterine device (IUD) or intrauterine system (IUS).

3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.

In case of use of oral contraception women should have been stable on the same pill for a
minimum of 3 months before taking study treatment. Postmenopausal females must have had no
regular menstrual bleeding for at least one (1) year prior to initial dosing. Menopause
will be confirmed by a plasma FSH level of > 40 IU/L (or as determined by the cut off used
by the local clinical laboratory) at screening. Female patients who report surgical
sterilization must have had the procedure at least six (6) months prior to initial dosing.
Surgical sterilization procedures should be supported with clinical documentation made
available to the sponsor and noted in the Relevant Medical History / Current Medical
Conditions section of the eCRF. All female patients must have negative pregnancy test
results at screening and baseline.

- Use of oral beta agonists, oral corticosteroids, androgens or androgen inhibitors
(including LHRH agonists), or intravenous gamma globulin (IVIG) within the previous 6
months. Short-term corticosteroids for unrelated indications, defined as < 20 mg/d for
< 30 days and ending at least 60 days prior to screening, are acceptable.

- Patients with known bleeding disorders, or who are under treatment with
anti-coagulants.

- A presence or history of clinically relevant ECG abnormalities, or including but not
limited to Long QT syndrome, ischemic changes that cannot be shown to be stable for at
least 6 months by previous ECG, or 2nd degree Mobitz II or 3rd degree heart block.

- History of malignancy of any organ system (other than localized basal cell carcinoma
of the skin), treated or untreated, within the past 5 years, regardless of whether
there is evidence of local recurrence or metastases.

- Significant illness which has not resolved within two (2) weeks prior to initial
dosing.

- A positive HIV, Hepatitis B surface antigen or Hepatitis C test result. No additional
exclusions may be applied by the investigator, in order to ensure that the study
population will be representative of all eligible patients.