INJECTABLE COLD ENERGY THERAPY FOR THE MANAGEMENT OF CHRONIC PAIN ASSOCIATED WITH OSTEOARTHRITIS OF THE KNEE

Inclusion Criteria:

1. Age 22 to 80, inclusive of any gender

2. Baseline pain intensity of >/= 5 of the Numeric Rating Scale (NRS) despite currenttreatment Confidential Brixton Biosciences Inc. Page 12 of 53 Version: 1.1, 30August 2024

3. Chronic symptomatic osteoarthritis of the knee (K-L stage 2, 3, or 4) on plainx-rays obtained within the previous 12 months

4. At least 3 months of previous conservative treatments (NSAID, acetaminophen,physical therapy, cortisone injections) that are not currently providing relief

5. Agree to see one doctor (study investigator) for knee pain during the study period

6. Willing/able to understand the informed consent form and provide written informedconsent

7. Able to complete outcome measures (including electronic patient reported outcomemeasures)

Exclusion Criteria:

1. Known allergy to glycerol, hyaluronic acid, poloxamer 407, or phosphate bufferedsaline

2. History of cryoglobulinemia

3. History of cold-induced auto-immune hemolytic anemia (e.g. paroxysmal coldhemoglobinuria or cold agglutinin disease)

4. History of cold urticaria

5. History of Chilblain's (pernio) disease in the lower extremities

6. History of Raynaud's disease

7. Open and/or infected wounds or active tumor at or near the treatment site

8. History of vascular surgery involving femoral vessels on the injection side

9. History of surgical procedures to affected limb that, in the opinion of theinvestigator, could have impacted the integrity of the genicular nerves or bloodvessels

10. Active bacterial or fungal infection that at the discretion of the investigatorwould preclude study participation

11. Currently taking >60 MME/day, as determined per MDcalc.com (opioid conversioncalculator)

12. History of History of systemic inflammatory conditions such as rheumatoid arthritis

13. Bleeding disorders anticoagulant therapy, unless appropriately stopped or reversedfor the procedure

14. Any condition or circumstance that would impact or confound assessment of safetyand/or pain. For example, comorbid or concomitant pain conditions, pre-existinglower limb neurologic deficits, any psychiatric or neurologic disease

15. Cryoneurolysis, thermal or pulsed radiofrequency ablation, or phenol injection forthe index knee within the past 12 months

16. Use of intra-articular injection of corticosteroid within the previous 3 months, orhyaluronic acid, prolotherapy, Confidential Brixton Biosciences Inc. Page 13 of 53Version: 1.1, 30 August 2024 autologous blood, or platelet rich plasma injectionsfor the index knee within the previous 6 months

17. Known contraindication to use of a regional anesthetic block

18. Pregnant, nursing or intent of becoming pregnant during the study period

19. Any condition (such as history of significant cardiovascular, renalfailure/dialysis, hepatic or other systemic comorbidity/chronic pain condition) orcircumstance that, in the opinion of the investigator, would compromise the safetyof the subject or the quality of study data

20. Body habitus/knee anatomy that would preclude the use of the product injectionneedle size

21. Participation in any clinical study of a therapeutic investigational product within 30 days prior to enrollment

22. Unwilling to refrain from participation in any other clinical study through theduration of this study

23. Unwilling to refrain from any scheduled surgeries during the duration of this study