Efficacy and Safety of TYRA-300 in Participants With FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer

Inclusion Criteria:

• Participants age 18 and over of informed consent and willing and able to comply withall requires study procedures

• Able to understand and given written informed consent

• Participants with histologically confirmed low-grade NMIBC within 6 weeks prior torandomization with prior diagnostic biopsy/TURBT to confirm stage and grade and withat least 3 mm and no more than 12 mm total (1/2 a resectoscope loop to 2 loops,refer to Section 8.1.5) residual visible tumor as a marker lesion(s) left behind:

1. Ta low grade

2. T1 low grade

• Participants must have intermediate risk NMIBC, defined as having any of thefollowing characteristics (AUA Guidelines, 2024)

1. Recurrence within 1 year, LG Ta

2. Solitary LG Ta >3cm

3. LG Ta, multifocal

4. LG T1

• Documented activating FGFR3 mutation or fusion (Appendix 4)

• Have undergone bladder mapping and identification of visible marker lesion(s) within 6 weeks prior to randomization (refer to Inclusion Criterion #3)

• No evidence of urothelial carcinoma of the upper urinary tract (confirmed byimaging) or prostatic urethra within 6 months of randomization

• No prior BCG administration within 1 year of date of consent.

• No intravesical chemotherapy within 8 weeks prior to C1D1.

• ECOG 0-1

• Pathology consistent with pure urothelial carcinoma; if mixed histology, ensure thatat least 80% of the sample is urothelial

• Adequate bone marrow, liver, and renal function: b. Bone marrow function: i. Absolute neutrophil count (ANC) > or = 1,500/mm3 ii.Platelet count > or = 75,000/mm3 iii. /hemoglobin > or = 10.0 g/dL e. Liverfunction: i.Total bilirubin < or = ULN ii. Alanine aminotransferase (ALT) < or = ULNiii. Aspartate aminotransferase (AST) < or = ULN f. Renal function: i. estimatedglomerular filtration rate >60 mL/min calculated using the modification of diet inrenal disease equation or CKD-EPI formula ii. Serum Phosphate level < or = ULN priorto starting treatment g. Coagulation i. International normalized ratio (INR) < or = 1.5 x ULN

• Ability to swallow tablets

• Participants (male and female) of child-bearing potential (including females who arepost-menopausal for less than 1 year) must be willing to practice effectivecontraception while on treatment and be willing and able to continue contraceptionfor 3 months (males) and 6 months (females) after the last dose of study treatment.Potential male participants should consider the potential impact of TYRA-300 ontheir ability to father a child and discuss options with the site study staff.

• Potential participants who are positive for human immunodeficiency virus (HIV) musthave a viral load below the limits of detection and on stable antiretroviral therapyfor at least 3 months prior to C1D1. NOTE: some of the compounds in antiretroviraltherapy may be on the prohibited medications list. Allowances will be made to ensurethe participant's HIV treatment continues uninterrupted following a discussion withthe Sponsor's medical monitor. A discussion of the impact of the antiretroviraltherapy on TYRA- 300 needs to be discussed with the potential participant prior toC1D1.

• Potential participants with chronic hepatitis B virus (HBV) infection with activedisease should be on a suppressive antiviral therapy prior to C1D1.

• Potential participants patients with a history of hepatitis C virus (HCV) infectionshould have completed curative antiviral treatment and must have a HCV viral loadbelow the limit of quantification.

• Potential participants with a history of HCV infection and on current treatment musthave a HCV viral load below the limit of quantification

Exclusion Criteria:

• Presence of tumor in ureter or prostatic urethra:

• Current or previous history of muscle invasive bladder cancer

• Current or previous history of lymph node positive and/or metastatic bladder cancer

• Evidence of pure squamous cell carcinoma, pure adenocarcinoma or pureundifferentiated carcinoma of the bladder

• Currently receiving systemic cancer therapy (cytotoxic, immunotherapy, targeted)

• Currently receiving treatment with a prohibited therapy (refer to Section 6.7.1)

• Current or prior history of pelvic external beam radiotherapy

• Current or history of receiving a prior FGFR inhibitor

• Systemic immunotherapy within 6 months prior to randomization

• Treatment with an investigational agent within 30 days or 5 half-lives fromrandomization, whichever is shorter; compounds with an unknown half-life willdefault to the 30 days.

• Prior treatment with an intravesical agent within 8 weeks prior to C1D1

• Current ongoing toxicity from previous therapy

• Had major surgery within 4 weeks prior to C1D1

• Any reason that in the view of the investigator, would substantially impair theability of the participant to comply with study procedures and/or risk to theparticipant (i.e., uncontrolled diabetes)

• Females who are pregnant, breastfeeding or planning to become pregnant within 6months after the last dose of TYRA-300 and males who plan to father a child whileenrolled in this study or within 3 months after the last dose of TYRA-300

• Has impaired wound healing capacity

• Serum phosphate levels above the upper limit of normal during screening

• Any ocular condition likely to increase the risk of eye toxicity

• Current evidence of central serous retinopathy or retinal pigmented epithelialdetachment of any grade at time of baseline examination.

• History of or current uncontrolled cardiovascular disease

• Gastrointestinal disorders that will affect oral administration or absorption ofTYRA-300

• Known history of HIV infection, or active hepatitis B or C

• History of a second primary malignancy within 3 years of signing ICF, except fornonmelanoma skin cancer and cured and active surveillance malignancies (i.e.,prostate, breast) .

• Known allergy to TYRA-300 or any excipients of the formulated product

• Participants taking strong inhibitors and/or inducers of CYP3A4 enzyme

• History of prolonged QT syndrome or baseline heart rate-corrected QT interval usingFridericia formula (QTcF) interval >470 ms