The Galvanize Therapeutics Early Stage, Non-Small Cell Lung Cancer, Treat and Resect Study

Lung cancer is the most common cancer in men and the third most common cancer
in women. NSCLC is the most common type of lung cancer, accounting for roughly
84% of all lung cancer diagnoses, 40% of which present at an advanced stage
[Jemal 2007], including locally advanced and metastatic disease [Cancer Facts &
Figures, ACS]. Early stage NSCLCs are generally not very sensitive to
chemotherapy and are treated through surgical resection with curative intent
when possible. Outcomes following surgical resection for small NSCLCs are good
with one-year survival rates of > 90% and five-year survival generally ranging
from 50-70% [van den Berg 2015]. While surgical resection results in the best
long-term outcomes for early stage NSCLC (in comparison to radiation,
chemotherapy, or ablation), not all patients are candidates for the procedure
due to tumor location, tumor progression, comorbidities, and other reasons
leaving a significant unmet need. Available treatment options for non-surgical
candidates include conventional chemotherapy, radiation, and focal ablation.

Unfortunately, despite the development of additional treatments, the overall
survival rate for NSCLC has only slightly improved over the last 30 years from
13% in the 1970*s to 21.7% in 2019 [American Lung Association, State of Lung
Cancer 2019]. Recently, molecular targeted therapies have shown promise in
improving outcomes, however, these treatments are only beneficial in subsets of
tumors with the appropriate genomic alteration. Additionally, advances in
immunotherapy have highlighted the potential of immune oncology-based
treatments for NSCLC, however, only a small percentage of patients actually
respond to treatment. Thus, there remains a significant unmet need to provide
more effective therapeutic
strategies to further improve outcome in patients with NSCLC.

The delivery of pulse electric fields (PEF) represents a novel technique that
is currently being researched for several clinical indications. The delivery of
PEFs can induce cell death via the delivery of high frequency short duration
electrical energy which disrupts the cell membrane
and the cells* ability to maintain homeostasis. One form of PEF technology
known as the NanoKnife® Tissue Ablation System (AngioDynamics Inc.) is
commercially available for the surgical ablation of soft tissue and is used for
the treatment of various inoperable or difficultto-reach tumors. Compared to
other ablative modalities used in the lung (i.e.radio-frequency, microwave,
cryotherapy), PEF ablation can induce cell death in a non-thermal manner which
has several potential benefits including an improved safety profile and ability
to treat lesions near critical structures due to the preservation of the
surrounding architecture including vessels, lymphatics, and the extracellular
matrix.

Further, cell death induced by PEF treatment may lead to enhanced efficacy
through stimulation of the body*s natural immune response. As opposed to
thermal ablative mechanisms, the non-thermal cell death induced by PEFs
releases a greater pool of antigens from the tumor which are accessible to
cells of the immune system. Additionally, limited encapsulation and scarring of
the treated area allows better access to these antigens and the tumor itself
for the immune cells, potentially enhancing the body*s innate and adaptive
response to the tumor. A similar but modified PEF treatment to that described
herein is also being studied in the lung for a chronic bronchitis indication. A
recently published study reported a very good safety profile, with significant
reductions in goblet cell hyperplasia and chronic bronchitis symptoms [Valipour
2020].

In this treat and resect study, PEF energy will be delivered to a solitary,
operable, NSCLC lesion prior to surgical resection. The PEF treatment will be
adjunctive to standard of care treatment that the patient would normally
receive for their NSCLC and occur within the usual timelines approximately 30
days from diagnostic procedure to surgical resection) for these early stage
NSCLC patients. This treat and resect study design allows for an evaluation of
the safety, feasibility, and initial clinical utility of the approach without
impacting standard of care treatment and provides a unique opportunity to
resect the tissue which has received PEF treatment to determine whether this is
a viable treatment option for NSCLC patients.

To evaluate the safety and initial feasibility of PEF treatment of NSCLC tumors
prior to surgical resection.

A prospective, two-arm, non-randomized, concurrently controlled, multi-center,
open-label, treat and resect study

Treatment may be delivered via either an endoluminal (bronchoscopic) or
percutaneous approach at the discretion of the clinical investigator utilizing
two available device configurations:
- Endoluminal: Galvanize Aliya System with commercially available TBNA Needle
(e.g., PeriView FLEX) and RF probe electrode
- Percutaneous: Galvanize Aliya System with compatible commercially available
RF needle and RF probe electrode

There are potential risks and side effects associated with the Galvanize PEF
procedure.

Risks potentially associated with participation in the study include the
following:
Endoluminal Procedures
• Sore throat (likely occurrence)
• Coughing (likely occurrence). Coughing up small amount of phlegm (mucous) is
common for 24 hours after the procedure. Coughing may continue for more than 24
hours.
• Hemoptysis (likely occurrence)
• Infection (moderately likely occurrence) including fever, pain or soreness
• Increase respiratory symptoms (moderately likely occurrence) including
shortness of breath, increased color and/or quantity of phlegm, cough, wheeze
or chest tightness
• Bronchial perforation (low occurrence)
• Lung abscess (low occurrence)
• Pneumothorax (low occurrence)
• Airway stenosis, scarring or injury (low occurrence) including wheezing,
hoarseness, shortness of breath and/or respiratory distress
• Significant pulmonary bleeding (low occurrence)
• Death (low occurrence)

Percutaneous Procedures
• Coughing (likely occurrence). Coughing up small amount of phlegm (mucous) is
common for 24 hours after the procedure. Coughing may continue for more than 24
hours.
• Chest pain, non-cardiac (likely occurrence)
• Pneumothorax (likely occurrence),
• Air embolism (low occurrence)
• Bleeding/hemorrhage or hemothorax (low occurrence)
• Infection (moderately likely occurrence) including fever, pain or soreness
• Bronchial perforation (low occurrence)
• Lung abscess (low occurrence)
• Hemoptysis (low occurrence)
• Airway stenosis, scarring or injury (low occurrence) including wheezing,
hoarseness, shortness of breath and/or respiratory distress
• Significant pulmonary bleeding (low occurrence)
• Death (low occurrence)

Other Risks
• Shortness of breath (likely occurrence)
• Gastroparesis (low occurrence)
• Abnormal cardiac rhythm function (low occurrence) including arrhythmia,
atrial fibrillation, ventricular fibrillation,
• Allergic reaction (low occurrence) including abnormal breathing, difficulty
swallowing, anxiety, chest pain, severe cough, lightheadedness or dizziness,
sweating or fainting, swelling of the face, eyes or tongue
• Fistula (low occurrence)
• Reflex hypertension (low occurrence)
• Thrombosis (low occurrence)
• Risk of anesthesia (likely occurrence) include, nausea, vomiting, bruising at
injection sites, sore throat, hoarse voice, damage to teeth, aspiration,
urinary retention, myocardial infarction, respiratory failure, brain damage,
and death, post bronchoscopy pain, drowsiness, slurred speech, tremor, fatigue,
low blood pressure, increased carbon dioxide in your blood, slowing of the
heart rate, anxiety, confusion, dizziness, shivering, bronchospasms,
respiratory depression, and changes in liver or heart function.
• Death (low occurrence)

Note: *Likely occurrence* refers to risks estimated to occur in more than more
than 10% of patients. Risks with *moderately likely occurrence* are estimated
to occur in 1 in 100 (1%), to 1 in 10 (10%) patients. Risks with *low
occurrence* are estimated to occur in less than 1 in 100 (1%) patients.

Other potential risk from study related tests and procedures include the
following:
• Blood draws: Mild pain, local irritation, bleeding or bruising (a black and
blue mark) at the puncture site. While rare, there is a possibility of
infection or a local blood clot with any procedure in which the skin is pierced
with a needle.
• CT Scan: Feeling of claustrophobia while performing the test. X-rays include
some amount of radiation which may increase the risk for cancer, although
unlikely.
o The effective radiation dose from one of these scans is about 4.5 mSv, which
is about the same as an average person receives from background
radiation in 1.2 years.
• Biopsy: Bleeding, coughing up small amounts of blood or blood-tinged sputum,
pneumothorax, or scarring of the area where the biopsy was taken
• Bronchoalveolar Lavage (BAL): Risks are similar to bronchoscopy procedures
including transient hypoxemia, fever, bronchospasm, and very rarely,
pneumothorax

The information gained from this study could result in improved management and
outcomes for NSCLC patients. No additional clinical benefit is expected beyond
that which if provided through surgical resection.
While all interventional clinical studies pose some risks to study
participants, the study sponsor has undertaken every effort to ensure that
risks are minimized. Based on prior literature, pre-clinical animal studies,
and prior PEF clinical experience, Galvanize Therapeutics, Inc. expects the
Galvanize Aliya System to be safe for the use in this clinical study.