Any thickness. Cohesive Fused, branching, and delicate Predominantly ordered, yet minimal crowding and minimal loss of polarity. Any thickness. Cohesive Fused, branching and delicate Predominantly disordered with frequent loss of polarity. An y thickness. Often discohesive Cytology: Nuclear size Nuclear shape Nuclear chromatin Nucleoi Mitoses Umbrella cells Identical to Normal Identical to Normal Fine Absent Absent Uniformly present May be uniformly enlarged Elongated, round - oval, uniform Fine Absent to inconspicuous Rare, basal Present Enlarged with variation in size Round -oval. Slight variation in shape and contour. Mild variation Usually inconspicuous* Occasionally at any level Usually present Enlarged with variation in size Moderate -marked pleomorphism Moderate -marked variation both within and between cells with hyperchromasia Multiple prominent nucleoli may be present Usually frequent, at any level May be absent *If present, small and regular and not accompanied by other features of high -grade carcinoma. Note: Only patients with high -risk disease (T1 and/or high grade and/or CIS) or intermediate -risk disease (Ta low grade with at least 3 of the following 4 risk factors: multiple tumors, tumor size >3cm, early recurrence (<1 year from previous TURBT), or frequent recurrences (>1 per year) ) are eligible for participation in the trial . Heat Biologics, Inc. Investigational Product: Vesigenurtacel -L Protocol HS410 -101 CONFIDENTIAL Version 8.0; 03 Feb 2016 Page 73 of 86 APPENDIX 2: STAGES OF HEART FAILURE The following stages of heart failure are based on the New Yo rk Heart Association (NYHA) functional classification system (taken from the Heart Failure Society of America http://www.abouthf.org/questions_stages.htm) . Class Patient Symptoms Class I (Mild) No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, or dyspnea (shortness of breath). Class II (Mild) Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea. Class III (Mode rate) Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV (Severe) Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency a t rest. If any physical activity is undertaken, discomfort is increased. Heat Biologics, Inc. Investigational Product: Vesigenurtacel -L Protocol HS410 -101 CONFIDENTIAL Version 8.0; 03 Feb 2016 Page 74 of 86 APPENDIX 3: GRADING SCALE FOR INJECTION SITE REACTIONS The grading scale is derived from the FDA Guidance for Industry (http://www.fda.gov/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/vac cin es/ucm074775.htm#TOXICITYGRADINGSCALETABLES ) Grade 1 Mild Grade 2 Moderate Grade 3 Severe Grade 4 Potentially Life Threatening Pain Does not interfere with activity Repeated use of non-narcotic pain reliever > 24 hours or interferes with activity Any use of narcotic pain reliever or prevents daily activity Emergency room visit or hospitalization Tenderness Mild discomfort to touch Discomfort with movement Significant discomfort at rest Emergency room visit or hospitalization Erythema/Redness 2.5-5 cm 5.1-10 cm > 10 cm Necrosis or exfoliative dermatitis Induration/Swelling* 2.5-5 cm and does not interfere with activity 5.1-10 cm or interferes with activity > 10 cm or prevents daily activity Necrosis * Induration/Swelling should be evaluated and graded using the functional scale as well as the actual measurement. Heat Biologics, Inc. Investigational Product: Vesigenurtacel -L Protocol HS410 -101 CONFIDENTIAL Version 8.0; 03 Feb 2016 Page 75 of 86 APPENDIX 4: PROTOCOL REVISION HISTORY Protocol Change Section Affected Version where implemented Change tumor volume collection from mg to ug (microns) Section 10.1.5 Version 2.0, Amendment 1 Allow immune monitoring to be either by flow cytometry or ELISPOT to determine best methodology to advance into Phase 2 Synopsis and Section 10.1 Version 2.0, Amendment 1 Add ELISPOT assay details Section 10.1.1 Version 2.0, Amendment 1 Remove the vial label from the protocol due to the potential for label changes over time Appendix 4 Version 2.0, Amendment 1 Clarify in inclusion criteria that bladder risk assessment score must be ≥8 on the recurrence scale and ≤ 18 on the progression sc ale Synopsis and Section s 4.1 and 6.2.1 Version 2.0, Amendment 1 Update timing of first dose relative to TURBT procedure to be consistent with the text elsewhere in the protocol Schedule of Events (SOE) Version 2.0, Amendment 1 Change DLT definition such that any AE >= Grade 3 that is possibly, probably, or definitely related to study drug be classified as such. (Formerly it was only "definitely" related items.) Also exceptions for systemic injections now ONLY include fever, my algia, headache, or fatigue, nothing additional.