ORIC-533 / ORIC Pharma - LARVOL DELTA

Preliminary Results of the Oral CD73 Inhibitor, Oric-533, in Relapsed/Refractory Multiple Myeloma (RRMM) (ASH 2023) - P1 | "ORIC-533 has demonstrated an acceptable safety profile and preliminary evidence of immune activation in a heavily pretreated RRMM patient population. Enrollment is ongoing and updated data will be presented."

Fatigue • Hematological Malignancies • Multiple Myeloma • Oncology • CD73 • CD8 • NT5E

Discovery of ORIC-533, an Orally Bioavailable CD73 Inhibitor That Maintains Activity in High AMP Environments to Reverse Tumor Immunosuppression. (PubMed, J Med Chem) - "Oral dosing of 6 reduces the concentration of ADO in the tumor microenvironment with a concomitant increase in CD8+ cells, resulting in tumor growth inhibition in a syngeneic mouse model of cancer. The strong potency and oral bioavailability support a potential best-in-class profile for 6, a CD73 inhibitor that entered phase 1b in patients with multiple myeloma."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • CD73 • CD8

ORIC-533-01: Study of ORIC-533 in Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=31 | Completed | Sponsor: ORIC Pharmaceuticals | Active, not recruiting ➔ Completed | N=56 ➔ 31 | Trial completion date: Sep 2024 ➔ Mar 2025 | Trial primary completion date: Sep 2024 ➔ Mar 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

ORIC-533-01: Study of ORIC-533 in Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=56 | Active, not recruiting | Sponsor: ORIC Pharmaceuticals | Recruiting ➔ Active, not recruiting | Phase classification: P1b ➔ P1 | Trial completion date: Jun 2024 ➔ Sep 2024 | Trial primary completion date: Jun 2024 ➔ Sep 2024

Enrollment closed • Phase classification • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

A novel small molecule inhibitor of CD73 triggers immune-mediated multiple myeloma cell death. (PubMed, Blood Cancer J) - P1b | No abstract available

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • CD73

Discovery of ORIC-533, an orally bioavailable CD73 inhibitor with best-in-class profile (ACS-Sp 2024) - P1b | "Utilizing ex vivo bone marrow-derived assays from patients with relapsed or refractory MM, ORIC-533 significantly increased immune cell cytotoxicity and reduced autologous myeloma tumor cell viability. Based upon these promising preclinical data, ORIC-533 is being evaluated in Phase 1b clinical trials in patients with relapsed or refractory MM (NCT05227144) and preliminary clinical PK and PD results will be shown."

Hematological Malignancies • Multiple Myeloma • Oncology • CD73 • CD8 • NT5E • PSAP

ORIC Pharmaceuticals Reports Fourth Quarter and Full Year 2023 Financial Results and Operational Updates (GlobeNewswire) - "Fourth Quarter 2023 and Other Recent Highlights: (i) ORIC-114:...Expect to initiate dose expansion of Phase 1b trial in multiple cohorts in the first half of 2024 and expect to report updated Phase 1b data in the first half of 2025; (ii) ORIC-944:...Expect to initiate combination study with AR inhibitor(s) in the first half of 2024 and provide a program update in mid-2024; (iii) ORIC-533:...Expect to complete dose escalation for the Phase 1b trial of ORIC-533 in the first quarter of 2024..."

New P1 trial • New trial • Trial status • Multiple Myeloma • Solid Tumor

Initial Phase 1 Dose Escalation Data for ORIC-533 in Relapsed/Refractory Multiple Myeloma Demonstrates Clinical Activity and Strong Safety Profile Supporting Potential for Combination Development (GlobeNewswire) - P1b | N=56 | NCT05227144 | Sponsor: ORIC Pharmaceuticals | "ORIC Pharmaceuticals...announced initial data from the ongoing ORIC-533 Phase 1 dose escalation trial in patients with relapsed/refractory multiple myeloma at the 65th American Society of Hematology (ASH) Annual Meeting....As of November 28, 2023, a total of 23 patients with multiple myeloma received doses ranging from 400 mg to 2400 mg once daily.....ORIC-533 demonstrated a favorable pharmacokinetic profile with an estimated plasma half-life of ~24 hours, which supports QD dosing....ORIC-533 exhibited clear evidence of immune activation in the majority of patients dosed at ≥ 1200 mg, as evidenced by an increased abundance and fraction of activated CD8+ T cells and NK cells. At the 1600 mg dose, there were notable reductions in soluble BCMA levels in serum, indicating that ORIC-533 was having a measurable antimyeloma effect....The company intends to complete dose escalation for ORIC-533 in the first quarter of 2024."

P1 data • Trial status • Multiple Myeloma

Study of ORIC-533 in Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1b | N=56 | Recruiting | Sponsor: ORIC Pharmaceuticals | Trial primary completion date: Jun 2023 ➔ Jun 2024

Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

ORIC Pharmaceuticals to Present Initial Phase 1b Clinical Data for ORIC-533 in Multiple Myeloma at the 65th American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - P1b | N=56 | NCT05227144 | Sponsor: ORIC Pharmaceuticals | "ORIC-533 was well tolerated with the vast majority of treatment-related adverse events (TRAEs) Grade 1 or 2 in severity and with no dose limiting toxicities, no Grade ≥ 4 TRAEs, and no treatment-related serious adverse events. ORIC-533 demonstrated good bioavailability and a plasma half-life of ~24 hours. Strong inhibition of soluble CD73 enzymatic activity was seen across all dose levels."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

ORIC Pharmaceuticals Reports Second Quarter 2023 Financial Results and Operational Updates (GlobeNewswire) - "ORIC-533: a highly potent, orally bioavailable small molecule inhibitor of CD73: (i) Ongoing enrollment in a Phase 1b trial of ORIC-533 in patients with relapsed/refractory multiple myeloma; (ii) Expect to report initial safety, PK/PD, and preliminary antitumor activity data in the fourth quarter of 2023."

Enrollment status • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

ORIC Pharmaceuticals Announces $85 Million Private Placement Financing (GlobeNewswire) - "ORIC Pharmaceuticals, Inc...has agreed to sell approximately 12.1 million shares of its common stock (or pre-funded warrants in lieu thereof) to a select group of institutional and accredited healthcare specialist investors in a private placement, at a price per share of $7.00, representing a premium of approximately 15% to ORIC’s 30-day volume-weighted average price and approximately 8% to the closing price on June 23, 2023. The pre-funded warrants will have an exercise price of $0.0001 per share of common stock, will be immediately exercisable, and will remain exercisable until exercised in full. The financing is expected to close on June 27, 2023, subject to customary closing conditions. ORIC anticipates the gross proceeds from the private placement to be approximately $85 million, before deducting any offering related expenses."

Financing • Genito-urinary Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Prostate Cancer • Solid Tumor

ORIC Pharmaceuticals Announces $85 Million Private Placement Financing (GlobeNewswire) - "ORIC-114: Report initial safety, PK/PD, and preliminary antitumor activity data from ongoing single agent Phase 1b study in patients with EGFR/HER2-mutated cancers in the second half of 2023; ORIC-533: Report initial safety, PK/PD, and preliminary antitumor activity data from ongoing single agent Phase 1b study in patients with multiple myeloma in the second half of 2023; ORIC-944: Report initial safety, PK/PD, and preliminary antitumor activity data from ongoing single agent Phase 1b study in patients with prostate cancer in the first quarter of 2024."

P1 data • PK/PD data • Genito-urinary Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Prostate Cancer • Solid Tumor

ORIC Pharmaceuticals Provides Corporate Update and Highlights Key Upcoming Milestones (GlobeNewswire) - "ORIC anticipates the following upcoming milestones: ORIC-533: Report initial safety, PK/PD, and preliminary antitumor activity data from ongoing single agent Phase 1b study in patients with multiple myeloma in the second half of 2023; ORIC-114: Report initial safety, PK/PD, and preliminary antitumor activity data from ongoing single agent Phase 1b study in patients with EGFR/HER2-mutated cancers in the second half of 2023; ORIC-944: Report initial safety, PK/PD, and preliminary antitumor activity data from ongoing single agent Phase 1b study in patients with prostate cancer in the second half of 2023."

P1 data • Genito-urinary Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Prostate Cancer • Solid Tumor

ORIC Pharmaceuticals Announces Clinical Development Collaboration with Pfizer for ORIC-533 in Multiple Myeloma and Concurrent $25 Million Equity Investment by Pfizer (GlobeNewswire) - "ORIC Pharmaceuticals...announced that it has entered into a clinical development collaboration for a potential Phase 2 study of ORIC-533 in multiple myeloma with Pfizer and agreed to sell 5,376,344 of its common shares at a price of $4.65 per share to Pfizer for proceeds of approximately $25.0 million. The common shares were sold to Pfizer in a registered direct offering conducted without an underwriter or placement agent....Through the agreement, the parties plan to potentially advance ORIC-533 into a Phase 2 combination study with elranatamab, Pfizer’s investigational B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody in development for the treatment of multiple myeloma. ORIC will maintain full economic ownership and control of ORIC-533."

Commercial • Licensing / partnership • New P2 trial • Hematological Malignancies • Multiple Myeloma • Oncology

CD73 Inhibition Reverses Immunosuppression and Has Potential As an Immunomodulatory Therapy in Patients with Multiple Myeloma (ASH 2022) - "This study, together with our previous reports, confirms that CD73 inhibition can reduce adenosine generation, overcome immune suppression, and restore lysis of MM cells. Based on these results, ORIC-533 is being studied as a single agent in a Phase 1 clinical trial in patients with relapsed or refractory multiple myeloma."

Clinical • IO biomarker • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology • NT5E • SDC1

ORIC Pharmaceuticals Presents Preclinical Data Demonstrating ORIC-533 as a Potential Best-in-Class CD73 Inhibitor at the 64th American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "Key highlights from the presentation include: Preclinical analyses continue to show ORIC-533 demonstrates a potential best-in-class CD73 inhibitor profile....ORIC-533 overcame immune suppression and triggered significant lysis of multiple myeloma cells across all dose levels tested and in a dose-responsive manner, in an autologous ex vivo assay using samples derived from bone marrow aspirates from patients with relapsed refractory multiple myeloma."

Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

ORIC Pharmaceuticals Reports Third Quarter 2022 Financial Results and Operational Update (GlobeNewswire) - "ORIC anticipates the following upcoming milestones: ORIC-533 (oral CD73 inhibitor): Initial Phase 1b data in 1H 2023, ORIC-114 (brain penetrant EGFR/HER2 exon 20 inhibitor): Initial Phase 1b data in 1H2023, ORIC-944 (allosteric PRC2 inhibitor): Initial Phase 1b data in 1H 2023."

P1 data • Genito-urinary Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Prostate Cancer • Solid Tumor

ORIC Pharmaceuticals to Present Preclinical Data on CD73 Inhibitor Program in Multiple Myeloma at the 64th American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "ORIC Pharmaceuticals...announced a preclinical poster presentation on ORIC-533 at the 64th American Society of Hematology (ASH) Annual Meeting to be held December 10-13, 2022, in New Orleans, LA...In autologous ex vivo assays using bone marrow aspirates from patients with relapsed refractory multiple myeloma, ORIC-533 overcame immune suppression and triggered significant lysis of multiple myeloma cells across all dose levels tested and in a dose-responsive manner."

Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor

ORIC Pharmaceuticals Reports Second Quarter 2022 Financial Results and Operational Update (GlobeNewswire) - "Three ongoing single agent Phase 1 programs, ORIC-533 in multiple myeloma, ORIC-114 in EGFR/HER2 cancers, and ORIC-944 in prostate cancer, all expected to report initial data in 1H 2023."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology • Prostate Cancer • Solid Tumor

ORIC-533, a small molecule CD73 inhibitor with best-in-class properties, reversesimmunosuppression and has potential as an immunomodulatory therapy in patients with multiple myeloma (AACR 2022) - "Recent clinical proof of concept data demonstrated a significant improvement in progression free survival for non-small cell lung cancer patients upon targeting CD73 with the oleclumab anti-CD73 antibody in combination with anti-PDL1, relative to anti-PDL1 checkpoint inhibitor treatment alone.We developed ORIC-533, a potent, orally bioavailable, AMP-competitive, small molecule inhibitor of CD73, that is highly selective for CD73 and exhibits picomolar potency in biochemical assays, completely blocking adenosine production from AMP. Taken together, these results demonstrate that the ORIC CD73 inhibitor potently inhibits the adenosine pathway, which restores anti-tumor immunity and therefore holds potential for patients with MM. Based upon these data, ORIC-533 is being studied as a single agent in a Phase 1 clinical trial in patients with relapsed or refractory multiple myeloma."

Clinical • IO biomarker • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8

Optimizations leading to ORIC-533: A potent orally bioavailable CD73 inhibitor that restores anti-tumor immunity in high AMP environments (AACR 2022) - "There is no abstract associated with this presentation."

Oncology

ORIC Pharmaceuticals Presents Promising Preclinical Data on Three Programs at the 2022 American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "...'Preclinical data further demonstrate the potential of CD73 inhibitor ORIC-533 as a treatment for multiple myeloma, as well as the compelling brain penetrant properties of ORIC-114 with its high potency against exon 20 insertion mutations. We also introduced our highly selective inhibitors of PLK4 as a potential treatment for breast cancer by leveraging a synthetic lethal liability. We look forward to the continued advancement of these programs as well as ORIC-944, with initial data for our three clinical programs expected in the first half of 2023'."

Clinical data • Preclinical • Synthetic lethality • Breast Cancer • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

ORIC Pharmaceuticals Reports Fourth Quarter and Full Year 2021 Financial Results and Operational Update (BioSpace) - "A Phase 1b trial with ORIC-533 as a single agent in multiple myeloma is enrolling patients and initial data are expected to be reported in the first half of 2023; A Phase 1b trial with ORIC-114 as a single agent has been initiated and will enroll patients with advanced solid tumors with EGFR or HER2 exon 20 alterations or HER2 amplification and will allow patients with CNS metastases that are either treated or untreated but asymptomatic. The company expects to report initial Phase 1b data from this trial in the first half of 2023; A Phase 1b trial with ORIC-944 as a single agent will enroll patients with metastatic prostate cancer. The company expects to report initial Phase 1b data from this trial in the first half of 2023."

P1 data • Trial status • CNS Tumor • Genito-urinary Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Prostate Cancer • Solid Tumor

ORIC Pharmaceuticals Announces Multiple Presentations at the 2022 American Association for Cancer Research (AACR) Annual Meeting (Yahoo Finance) - P1 | N=48 | NCT05227144 | Sponsor:Oric Pharmaceuticals | “ORIC Pharmaceuticals, Inc….announced three poster presentations and one oral presentation at the 2022 American Association for Cancer Research (AACR) Annual Meeting taking place April 8-13, 2022, in New Orleans, LA. The presentations will highlight preclinical data regarding two Phase 1 programs, including ORIC-533, a highly potent, orally bioavailable CD73 inhibitor, and ORIC-114, a brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations. The presentations will also introduce a new program targeting a synthetic lethality pathway in breast cancer.”

Clinical data • Preclinical • Breast Cancer • Lung Cancer • Multiple Myeloma • Non Small Cell Lung Cancer • Oncology • Solid Tumor