Study to Prevent Acute Kidney Injury After Cardiac Surgery Involving Cardiopulmonary Bypass

Angion Biomedica Corp. has developed a small molecule hepatocyte growth factor/scatter
factor (HGF/SF) mimetic, termed BB3, which exerts significant nephroprotective effects in
several preclinical renal injury models. Angion intends to develop BB3 as a therapy to
prevent and/or treat acute kidney injury. BB3 is a new molecular entity and the proposed
treatment is novel since no drug is currently available with an indication to prevent and/or
treat acute kidney injury.

This is a randomized, prospective, parallel-group, double-blind, placebo-controlled,
multicenter study. Patients who will be undergoing a surgical procedure involving CPB and
are at elevated risk pre-surgery for AKI will be eligible to participate in the study.
Patients will be randomized 1:1 to receive either BB3 or placebo (normal saline) immediately
after surgery. Study drug will be administered for a total of 4 daily intravenous (IV)
infusions. The first post-operative dose MUST be started within 4 hours of completing CPB.
The second dose will be administered 24 ± 2 hours after completing CPB, and the third and
fourth doses will be administered 24 ± 2 hours after each previous dose.

Patients will be followed for safety, PK (in a subset of patients), and efficacy up to Day
90, with Day 1 being the day of the first infusion of study drug. Patients will be assessed
daily through Day 7 and then on Days 14, 30 and 90.

Efficacy endpoints include assessment of post-CPB renal injury, expressed as percent
increase in sCr above Baseline over time and the maximum percent increase in sCr following
CPB, from 24 hours after end of CPB through Day 5; the proportion of patients reaching each
KDIGO stage or having no AKI at specified time points through Day 30; and analyses among
patients who develop AKI assessing time to recovery or reduction in KDIGO stage.

Approximately 100 patients will be randomized; 50 patients will be randomized to BB3 and 50
patients to placebo.

Inclusion Criteria:

1. Patient is either male or female ≥ 18 years.

2. Patient has provided written informed consent, and is willing and able to comply with
the requirements of the study protocol, including screening procedures.

3. Patient must be scheduled for and undergo a non-emergent cardiac surgical procedure
involving CPB. Eligible procedures include:

1. Coronary artery bypass graft (CABG) alone

2. Aortic valve replacement or repair alone, with or without aortic root repair

3. Mitral, tricuspid, or pulmonic valve replacement or repair alone

4. Combined replacement of several cardiac valves

5. CABG with aortic, mitral, tricuspid, or pulmonic valve replacement or repair

6. CABG with combined cardiac valve replacement or repair.

4. Patient must have the following risk factor(s) for AKI prior to surgery:

1. Estimated glomerular filtration rate (eGFR) of ≥ 20 and < 30 ml/min/1.73m2, or

2. eGFR ≥ 30 and < 60 mL/min/1.73m2 and ONE of the following Additional Risk
Factors (other than age ≥ 75 years), or

3. eGFR ≥ 60 ml/min/1.73m2 and TWO of the following Additional Risk Factors

eGFR will be calculated using the abbreviated MDRD equation (MDRD-4, often referred
to as the Levey equation): eGFR = 186.3 x sCr-1.154 x Age-0.203 x [0.742 if Female] x
[1.212 if Black]

Additional Risk Factors:

- Combined valve and coronary surgery

- Previous cardiac surgery with sternotomy

- Left ventricular ejection fraction (LVEF) < 35% by invasive or noninvasive
diagnostic cardiac imaging within 90 days prior to surgery

- Diabetes mellitus requiring insulin treatment

- Non-insulin-requiring diabetes with documented presence of at least moderate
(+2) proteinuria on urine analysis (medical history or dipstick)

- Documented NYHA Class III or IV within 1 year prior to index surgery

- Age ≥ 75 years can be considered an Additional Risk Factor only for patients
with eGFR ≥ 60 ml/min/1.73m2.

5. Patient must have presented for surgery without prior evidence of active renal injury
defined as no acute rise in sCr > 0.3 mg/dL or no 50% increase in sCr between the
time of Screening and pre-surgery.

6. Patient's body mass index (BMI) < 35 at Screening.

7. Female patients of childbearing potential (including perimenopausal women who have
had a menstrual period within 1 year):

1. Must have a negative serum pregnancy test prior to surgery.

2. Must agree (1) to use 2 forms of effective birth control regimen (at least
one-barrier method) during the 90-day study period or (2) to maintain total
abstinence throughout the 90-day study period.

8. Male patients must agree to use condoms or other suitable means of pregnancy
prevention such as abstinence during the 90-day study period.

Exclusion Criteria:

1. Patient has eGFR < 20 mL/min/1.73 m2 within 48 hours pre-surgery as measured by MDRD
4.

2. Patient has ongoing sepsis or partially treated infection. Sepsis is defined as the
presence of a confirmed pathogen, along with fever or hypoperfusion (i.e., acidosis
and new onset elevation of liver function tests) or hypotension requiring pressor use
prior to surgery.

3. Currently active infection requiring antibiotic treatment.

4. Patient who has an active (requiring treatment) malignancy or history of solid,
metastatic or hematologic malignancy with the exception of basal or squamous cell
carcinoma of the skin that has been removed.

5. Administration of iodinated contrast material within 48 hours prior to cardiac
surgery.

6. Patients diagnosed with AKI as defined by KDIGO criteria within 48 hours prior to
surgery.

7. Cardiogenic shock or hemodynamic instability within 24 hours prior to randomization,
defined as SBP < 80 mmHg and pulse > 120 beats/min and requirement for inotropes or
vasopressors or other mechanical devices such as IABP.

8. Need for any of the following within 7 days prior to surgery: defibrillator or
permanent pacemaker, mechanical ventilation, IABP, left ventricular assist device
(LVAD), or other form of mechanical circulatory support.

9. Required cardiopulmonary resuscitation within 7 days prior to cardiac surgery.

10. Female patient who is lactating or breast feeding.

11. Patient has history of positive human immunodeficiency virus (HIV) test.

12. Requires treatment with the cytochrome P450 1A2 (CYP1A2) inhibitors, ciprofloxacin
(Cipro®) and/or fluvoxamine (Luvox®).

13. Patient is unwilling or unable to comply with the protocol or to cooperate fully with
the Investigator or the site personnel.

14. Patient is not deemed medically stable for the study in the opinion of the
Investigator or the subject's primary nephrologist.

15. Patient with a clinical or laboratory diagnosis of shock liver.

16. Exclusion criteria during surgery:

Patients who have a procedure during surgery or experience an intra-operative complication
which, in the opinion of the Investigator, precludes dosing of the patient with study
drug; examples include implantation of an IABP or LVAD, acute myocardial infarction,
cardiac arrest during surgery, and procedure-associated decrease in ejection fraction.