BIO 300 Non-Small Cell Lung Cancer Study

This is an open-label, single-arm, ascending dose Phase I/II study of BIO 300 Oral Suspension
given in combination with paclitaxel/carboplatin and radiotherapy in subjects with stage II,
III, or IV NSCLC who are candidates for combined chemoradiotherapy.

A minimum of 6 subjects will be accrued sequentially at each dose level of BIO 300. BIO 300
will be administered daily for the entire course of concurrent chemoradiotherapy, a minimum
of 6 weeks; in combination with standard paclitaxel / carboplatin chemotherapy and
radiotherapy.

The initial dose of BIO 300 will be administered on Day 1, Visit 2 in which safety data
(adverse events, electrocardiograms (ECGs), results of safety laboratory determinations),
pharmacokinetic (PK) and pharmacodynamic (PD) data will be collected. PK data will be
collected from a minimum of six (6) study subjects from each cohort. PD data will be
collected from all subjects in each study cohort. Day 1 of chemotherapy will be scheduled at
the discretion of the investigator provided the subject has completed a minimum of 1 day of
BIO 300 dosing. BIO 300 will be administered in combination with the chemotherapy components
of the protocol (paclitaxel and carboplatin). During the first or second chemotherapy
infusion, additional safety, PK and PD data will be collected. Day 1 of radiation therapy
(RT) may be scheduled at the discretion of the investigator provided the subject has
completed a minimum of 2 days of BIO 300 dosing. BIO 300 will continue to be administered
daily; paclitaxel and carboplatin will be administered weekly and radiotherapy will be
administered daily until a total dose of 60-70 Gy has been administered. During the period of
combined BIO 300 and chemoradiotherapy (6-7 weeks), additional safety, PK and PD data will be
collected weekly. An interim data analysis will be completed once the highest dose cohort
concludes chemoradiation therapy, in an effort to determine the optimal biological dose.
Following analysis, there will be an option to enroll up to an additional 12 subjects at the
optimal biological dose. At the conclusion of the study, primary and secondary outcome
measures will be evaluated. Data will be analyzed from all cohorts to determine the oncologic
response, safety of BIO 300, and a recommended BIO 300 dose.

Inclusion Criteria:

1. Histological or cytological confirmation of NSCLC

2. Stage II, III, or IV NSCLC for whom radiation therapy of 60 Gy and concurrent weekly
paclitaxel/carboplatin is recommended

3. Up to three small (≤ 3 cm each) lung oligometastases will be allowed and/or one
oligometastasis at any other site in the body

4. Eastern Cooperative Oncology Group Performance Scale (ECOG PS) of 0 or 1

5. Forced expiratory volume at one second (FEV1): best value obtained pre- or
post-bronchodilator must be ≥ 1.0 liters/second or > 50% predicted value

6. Adequate bone marrow reserve

7. Adequate hepatic reserve

8. Adequate renal function

9. Female subjects of childbearing potential must have a negative pregnancy test

10. Female subjects of childbearing potential and male subjects with female sexual
partners of childbearing potential must agree to use an effective method of
contraception

11. Ability to read and provide written informed consent

Exclusion Criteria:

1. Weight loss greater than 10% in prior 4 weeks

2. Prior malignancy in which they received any thoracic radiotherapy unless the treating
physician considers it unlikely to impact the clinical outcome of the patient

3. Patients with concurrent invasive malignancy other than non-melanoma skin cancer or
cervical intraepithelial neoplasia unless the treating physician considers it unlikely
to impact the clinical outcome of the patient

4. An active infection or with a fever ≥ 38.5°C

5. Poorly controlled intercurrent illnesses

6. Patients with a prior thoracotomy within 1 week of study registration

7. Chronic Obstructive Pulmonary Disease (COPD) exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days before
registration

8. Patients with any of the following are not eligible:

- Previous history of Corrected QT Interval (QTc ) prolongation resulting from
medication that required discontinuation of that medication

- Congenital long QT syndrome, or 1st degree relative with unexplained sudden death
under 40 years of age;

- Presence of left bundle branch block (LBBB);

- QTc with Fridericia's correction that is unmeasurable, or ≥ 480 msec on screening
ECG. The average QTc from the screening ECG (completed in triplicate) must be <
480 msec in order for the patient to be eligible for the study;

- Subjects taking any concomitant medication that may cause QTc prolongation,
induce Torsades de Pointes are not eligible if QTc ≥ 460 msec.

9. Patients must not have had a clinically significant cardiac event within 6 months
before entry; or the presence of any other uncontrolled cardiovascular conditions
that, in the opinion of the Investigator, increases the risk of ventricular
arrhythmia.

10. Patients with a history of arrhythmia or asymptomatic sustained ventricular
tachycardia are not eligible. Patients with atrial fibrillation with well-controlled
ventricular rate on medication, are eligible.

11. Psychiatric conditions, social situations or substance abuse that precludes the
ability of the subject to cooperate with the requirements of the trial and protocol
therapy

12. Grade 2 or higher peripheral neuropathy

13. Known history of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome
(HIV/AIDS), hepatitis B or C.

14. Pregnancy or women of childbearing potential and men who are sexually active and not
willing/able to use medically acceptable forms of contraception

15. Women who are breastfeeding are not eligible for this study.