TRC253 / Tracon Pharma - LARVOL DELTA

Computational screening of FDA-approved drugs to identify potential TgDHFR, TgPRS, and TgCDPK1 proteins inhibitors against Toxoplasma gondii. (PubMed, Sci Rep) - "Also, the Pharmit software was used to generate pharmacophore models based on the TgDHFR complexed with TRC-2533, TgPRS in complex with halofuginone, and TgCDPK1 in complex with a bumped kinase inhibitor, RM-1-132. Ezetimibe, Raloxifene, Sulfasalazine, Triamterene, and Zafirlukast drugs against the TgDHFR protein, Cromolyn, Cefexim, and Lactulose drugs against the TgPRS protein, and Pentaprazole, Betamethasone, and Bromocriptine drugs against TgCDPK1 protein showed the best results. These drugs had the lowest energy-based docking scores and also stable interactions based on MD analyses with TgDHFR, TgPRS, and TgCDPK1 drug targets that can be introduced as possible drugs for laboratory investigations to treat T. gondii parasite infection."

FDA event • Journal • Infectious Disease • DHFR

An open-label phase 1/2a study to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of TRC253, an androgen receptor antagonist, in patients with metastatic castration-resistant prostate cancer (mCRPC). (ASCO-GU 2018) - P1/2; "Clinical trial information: NCT02987829Part 2 patients must have demonstrated acquired resistance to enzalutamide or apalutamide. Descriptive statistics will be used to summarize patient characteristics, safety, efficacy, PK, and immunologic biomarkers."

Clinical • P1/2 data • PK/PD data • Prostate Cancer

An open label phase 1/2A study to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of TRC253, an androgen receptor antagonist, in patients with metastatic castration-resistant prostate cancer. (ASCO 2019) - P1/2; "TRC253 daily at 280 mg was well-tolerated and selected as the RP2D. P2 dose expansion is currently enrolling 2 cohorts: 15 pts with AR F877L and 30 pts without AR F877L. The objectives of P2 include collection of additional data for safety, PK, PET and efficacy of TRC253 in mCRPC pts with specific AR mutations."

Clinical • P1/2 data • PK/PD data

Spirocyclic Thiohydantoin Antagonists of F877L and Wild-Type Androgen Receptor for Castration-Resistant Prostate Cancer. (PubMed, ACS Med Chem Lett) - "AR F877L, a point mutation in the ligand binding domain of the AR, was identified in patients who acquired resistance to enzalutamide or apalutamide. In parallel to our previous structure-activity relationship (SAR) studies of compound 4 (JNJ-pan-AR) and clinical stage compound 5 (JNJ-63576253), we discovered additional AR antagonists that provide opportunities for future development. Here we report a highly potent series of spirocyclic thiohydantoins as AR antagonists for the treatment of the F877L mutant and wild-type CRPC."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

Discovery of JNJ-63576253: A Clinical Stage Androgen Receptor Antagonist for F877L Mutant and Wild-Type Castration-Resistant Prostate Cancer (mCRPC). (PubMed, J Med Chem) - "The AR F877L mutation, identified in patients treated with enzalutamide or apalutamide, confers resistance to both enzalutamide and apalutamide. Metabolite identification studies revealed a latent bioactivation pathway associated with 4. Subsequent lead optimization of 4 led to amelioration of this pathway and nomination of 5 (JNJ-63576253) as a clinical stage, next-generation AR antagonist for the treatment of castration-resistant prostate cancer (CRPC)."

Clinical • Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

Discovery of JNJ-63576253, a next-generation androgen receptor antagonist active against wild-type and clinically-relevant ligand binding domain mutations in mCRPC. (PubMed, Mol Cancer Ther) - "In order to address this unmet need, we report the discovery of JNJ-63576253, a next-generation androgen receptor pathway inhibitor that potently abrogates AR signaling in models of human prostate adenocarcinoma. JNJ-63576253 is advancing as a clinical candidate with potential effectiveness in the subset of patients who do not respond to or are progressing while on 2nd-generation AR targeted therapeutics."

Clinical • Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Phase 1/2A Study of TRC253, an Androgen Receptor Antagonist, in Metastatic Castration-resistant Prostate Cancer Patients (clinicaltrials.gov) - P1/2; N=71; Completed; Sponsor: Tracon Pharmaceuticals Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

TRACON Pharmaceuticals retains global rights to TRC253 following completion of a phase 1/2 trial (GlobeNewswire) - “TRACON Pharmaceuticals…announced that it has retained global rights to and has sole responsibility for development and commercialization of TRC253 based on Janssen Pharmaceutica N.V.’s (Janssen’s) decision not to exercise its option to reacquire global rights to TRC253 following a review of the Phase 2 data in prostate cancer patients with acquired resistance to Xtandi® or Erleada®. Under the original agreement, TRACON is obligated to make certain payments to Janssen if future development and regulatory milestones are achieved and to pay a royalty on net sales of TRC253.”

Licensing / partnership • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer

TRACON Pharmaceuticals driving the development of targeted therapies for cancer (Proactiveinvestors) - "Proof-of-concept data from the Phase 1/2 trial of TRC253 in patients with metastatic prostate cancer expected in first half 2020."

P1/2 data

TRACON Pharmaceuticals Reports Fourth Quarter and Year-End 2019 Financial Results and Provides Corporate Update (GlobeNewswire, TRACON Pharmaceuticals, Inc.) - “Meet with FDA to discuss potential pivotal trial design for envafolimab, followed by the submission of an application for orphan drug designation, in the first half of 2020. Enroll the first patient in a potentially pivotal trial of envafolimab in sarcoma during the second half of 2020; Phase 2 proof-of-concept data from the fully enrolled Phase 1/2 clinical trial of TRC253 in metastatic castrate resistant prostate cancer are expected in the first half of 2020; Top-line data from the Phase 1 dose escalation study of TJ004309, a CD73 antibody, as a single agent and in combination with Tecentriq, a marketed PD-L1 antibody being supplied by Roche, are expected in the second half of 2020; Nomination and IND filing of the initial bispecific antibody (BsAb) from the I-Mab pipeline is expected in the second half of 2020. The I-Mab BsAb pipeline includes PD-L1 x IL-7, PD-L1 x CD47, PD-L1 x CD73, PD-L1 x B7-H3, and PD-L1 x 4-1BB antibodies.”

Clinical protocol • Enrollment status • IND • Orphan drug • P1 data • P1/2 data

Phase 1/2A Study of TRC253, an Androgen Receptor Antagonist, in Metastatic Castration-resistant Prostate Cancer Patients (clinicaltrials.gov) - P1/2; N=71; Active, not recruiting; Sponsor: Tracon Pharmaceuticals Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • KLK3

TRACON Pharmaceuticals reports third quarter 2019 financial results and provides corporate update (GlobeNewswire, TRACON Pharmaceuticals, Inc.) - "The Phase 2 POC data from the Phase 1/2 clinical trial of TRC253 in metastatic castrate resistant prostate cancer is now expected in the first half of 2020...Top line data for the Phase 1 dose escalation study of TJ004309, a CD73 antibody, as a single agent and in combination with Tecentriq, a marketed PD-L1 antibody being supplied by Roche, is expected in the second half of 2020."

P1 data • P2 data

Phase 1/2A Study of TRC253, an Androgen Receptor Antagonist, in Metastatic Castration-resistant Prostate Cancer Patients (clinicaltrials.gov) - P1/2; N=80; Recruiting; Sponsor: Tracon Pharmaceuticals Inc.; Trial completion date: Jun 2019 ➔ Oct 2020; Trial primary completion date: Jun 2019 ➔ Mar 2020

Trial completion date • Trial primary completion date

TRACON Pharmaceuticals reports second quarter 2019 financial results and provides corporate update (Tracon Pharmaceuticals Press Release) - “Expected Upcoming Milestones: Presentation of Phase 2 data from Phase 1/2 clinical trial of TRC253 in metastatic castrate resistant prostate cancer to Janssen is expected in the second half of 2020, whereupon Janssen will have an exclusive option to reacquire full rights to TRC253 for an opt-in payment of $45 million to TRACON, and obligations to pay regulatory and commercialization milestones totaling up to $137.5 million upon achievement of specified events and a low single-digit royalty on net sales.”

P2 data

Tracon Pharmaceuticals provides update on phase 1/2 trial of TRC253 in patients with metastatic castrate resistant prostate cancer (Tracon Pharmaceuticals Press Release) - P1/2, N=80; NCT02987829; Sponsor: Tracon Pharmaceuticals Inc; “Target PK exposures were achieved consistently with the 280 mg daily oral dose, which was selected as the recommended Phase 2 dose. The single patient with a F877L androgen receptor (AR) point mutation at baseline remained on treatment for 49 weeks with a partial response by RECIST. The remaining 20 patients did not have a F877L AR point mutation at baseline, and 48% (10) remained on study for at least 6 months and one patient had a greater than 50% decrease in prostate specific antigen (PSA). TRC253 was well-tolerated and no drug-related serious adverse events were reported. Drug-related adverse events included QTcF prolongation, elevated lipase, fatigue, arthralgia, diarrhea, and platelet count decrease….look forward to the availability of Phase 2 data, which we expect in the second half of 2020’…”

P1/2 data • P2 data

TRACON Pharmaceuticals reports first quarter 2019 financial results and provides corporate update (Tracon Pharmaceuticals Press Release) - "Expected Upcoming Milestones: Dosing of the first patient in a Phase 1 study of TJ004309 as a single agent and in combination with Tecentriq® (atezolizumab), a PD-L1 checkpoint inhibitor marketed by Roche, in patients with advanced solid tumors is expected mid-2019; Publication of TRC253 Phase 1 data in patients with metastatic castrate resistant prostate cancer is expected in the second quarter of 2019."

Enrollment status • P1 data

Antitumor activity of JNJ-63576253 (TRC253), a small molecule antagonist of F877L mutant and wild-type androgen receptor (AACR 2019) - "In male SHO mice bearing LNCaP xenografts with either wild-type or ARF877L, daily treatment with 30 mg/kg JNJ-63576253 treatment resulted in statistically significant antitumor activity, whereas second-generation antiandrogen enzalutamide had no antitumor efficacy in the LNCaP ARF877L mutant model.Janssen and Tracon Pharma have entered a strategic licensing collaboration, whereby Tracon possesses exclusive rights for clinical development of JNJ-63576253 (now called TRC253). Tracon has entered TRC253 into Ph1/2A clinical evaluation in metastatic castration-resistant prostate cancer patients."

TRACON Pharmaceuticals Announces TRC105, TRC253 and TRC102 Data Presentations at Upcoming AACR Annual Meeting (GlobeNewswire, TRACON Pharmaceuticals, Inc.) - TRACON Pharmaceuticals...announced that preclinical data from TRC105 and TRC253, as well as Phase 2 clinical data from TRC102, will be presented at the upcoming American Association for Cancer Research (AACR) annual meeting, to be held from March 29 to April 3, 2019, in Philadelphia, PA.

Late-breaking abstract • P2 data • Preclinical

TRACON Pharmaceuticals Reports Fourth Quarter and Year-End 2018 Financial Results and Provides Corporate Update (GlobeNewswire, TRACON Pharmaceuticals, Inc.) - "Expected Upcoming Milestones: Announcement of the results of the interim analysis to determine the final sample size of the Phase 3 pivotal TAPPAS trial of TRC105 in angiosarcoma is expected in April; Announcement of first in human dosing of TJ4309 is expected in the first half of 2019; Presentation of preclinical data by Leiden University researchers on the activity of TRC105 in combination with checkpoint inhibitors at the American Association for Cancer Research (AACR) annual meeting in Philadelphia, PA is expected in March; Presentation of expanded cohort data by the National Cancer Institute from the Phase 1 trial of TRC102 and Temodar in patients with colorectal, lung and ovarian cancer at the AACR annual meeting in Philadelphia, PA is expected in April; Presentation of TRC253 Phase 1 data in patients with metastatic castrate resistant prostate cancer is expected in the first half of 2019."

P1 data • P3 data • Preclinical • Trial status

TRACON Pharmaceuticals reports first quarter 2018 financial results and provides corporate update (GlobeNewswire) - "Presentation of data from preclinical studies of TRC105 in combination with PD-1 checkpoint inhibition at International Microenvironment Cancer Society meeting in June 2018 in Lisbon. Completion of the dose escalation portion of the Phase 1/2 trial of TRC253 in patients with prostate cancer in mid-2018...top-line data from...Phase 2 TRAXAR trial [NCT01806064] of TRC105...is expected in the second half of 2018...results of the interim analysis from the Phase 3...TAPPAS trial [NCT02979899] of TRC105 in angiosarcoma is expected in the second half of 2018. Presentation of data from the Phase 1b trial [NCT03181308] of TRC105 in combination with Opdivo in patients with non-small cell lung cancer is expected in the second half of 2018."

P1 data • P2 data • P3 data • Preclinical • Trial status

TRACON Pharmaceuticals reports fourth quarter and year-end 2017 financial results and provides corporate update (GlobeNewswire) - "Completion of the dose escalation portion of the Phase 1/2 trial of TRC253 in patients with prostate cancer is expected in mid-2018.; Announcement of top-line data from...Phase 2 TRAXAR trial of TRC105 in combination with Inlyta for patients with advanced or metastatic renal cell carcinoma is expected in mid-2018.; Announcement of the results of the interim analysis from the Phase 3 pivotal TAPPAS trial of TRC105 in angiosarcoma is expected in the second half of 2018.; Presentation of data from the Phase 1b trial of TRC105 in combination with Opdivo in patients with non-small cell lung cancer is expected in the second half of 2018."

P1 data • P2 data • P3 data • Trial status