INX-315 / Incyclix Bio, Pharmacosmos - LARVOL DELTA

Incyclix Bio Granted U.S. FDA Fast Track Designation for INX-315 to Treat CCNE1-Amplified Platinum-Resistant/Refractory Ovarian Cancer (GlobeNewswire) - "Incyclix Bio, LLC...today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for INX-315 for the treatment of CCNE1-amplified platinum-resistant/refractory ovarian cancer....INX-315 is a novel, potent and selective CDK2 inhibitor that is being evaluated in INX-315-01, an ongoing first-in-human Phase 1/2 clinical trial to evaluate its safety, tolerability, pharmacokinetics (PK) and preliminary antitumor activity in patients with recurrent advanced/metastatic cancer."

Fast track • Platinum resistant • Ovarian Cancer

INX-315-01: Open-Label Study to Evaluate the Safety, Tolerability, PK, and Efficacy of INX-315 in Patients With Advanced Cancer (clinicaltrials.gov) - P1/2 | N=150 | Recruiting | Sponsor: Incyclix Bio | N=90 ➔ 150

Enrollment change • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • CCNE1 • ER • HER-2

Targeting CDK2 in estrogen receptor-positive/RB-deficient breast cancer (AACR 2025) - "Notably, the therapeutic combination of INX-315 and fulvestrant (a selective ERα degrader) synergistically suppressed the growth of MCF7 RBKO xenografts and ER+/RB1-deleted patient-derived xenografts in mice. Treatment with this combination reduced Ki67 levels more potently than each monotherapy or vehicle. These findings collectively identify CDK2 as a promising therapeutic target for ER+/RB-deficient breast cancer and support clinical testing of CDK2- and ERα-tagerted combination therapies in this refractory population."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CDK2 • ER • RB1

Incyclix Bio Announces Publication in Nature Communications Highlighting Biomarkers of Response to CDK2 Inhibition (GlobeNewswire) - "The publication outlines the analysis of DEPMAP data utilizing the CHRONOS score to distinguish cell response based on their dependencies to cyclins and CDKs that regulate the G1 to S phase transition. This analysis segregated cell lines into distinct clusters demonstrating specific dependencies on various cyclin and CDK genes, revealing tumor types that are exceptionally dependent on CDK2 and more sensitive to the INX-315 CDK2 inhibitor....Based on the results of the analysis, a broader range of tumors, including both breast and pancreatic cancer models, respond to CDK2 inhibitors."

Preclinical • Breast Cancer • Pancreatic Cancer

Discrete vulnerability to pharmacological CDK2 inhibition is governed by heterogeneity of the cancer cell cycle. (PubMed, Nat Commun) - "CRISPR screens identify CDK2 loss as a mediator of resistance to a CDK2 inhibitor, INX-315...These include the depletion of mitotic regulators as well as CDK4/6 inhibitors cooperate with CDK2 inhibition in multiple phases of the cell cycle. Overall, this study underscores two fundamentally distinct features of response to CDK2 inhibitors that are conditioned by tumor context and could serve as the basis for differential therapeutic strategies in a wide range of cancers."

Heterogeneity • Journal • Breast Cancer • Oncology • Psychiatry • Solid Tumor • CCNB1 • CCNE1 • CDK1 • CDKN2A

INX-315, an oral, potent and selective CDK2 inhibitor in patients with CDK4/6 inhibitor resistant ER+/HER2- breast cancer or CCNE1 amplified solid tumors: phase 1 monotherapy dose escalation (SABCS 2024) - P1/2 | "INX-315 monotherapy at increasing QD dose levels was generally well tolerated and demonstrated monotherapy antitumor activity in heavily pretreated patients with ER+/HER2- breast cancer and CCNE1amplified solid tumors. Dose escalation and optimization is ongoing to determine the dose levels to be further evaluated in monotherapy (CCNE1 amplified HGSOC) and combination (ER+/HER2- breast cancer) expansion parts of the study."

Clinical • Monotherapy • P1 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CCNE1 • ER • HER-2

Incyclix Bio Announces Interim Clinical Data from the Phase 1/2 Clinical Trial of INX-315 in Patients with CDK4/6 Inhibitor Resistant ER+/HER2- Breast Cancer or CCNE1-Amplified Solid Tumors (GlobeNewswire) - P1/2 | N=90 | INX-315-01 (NCT05735080) | Sponsor: Incyclix Bio | "INX-315 monotherapy demonstrated antitumor activity in heavily pretreated patients with ER+/HER2- breast cancer and CCNE1-amplified ovarian cancer: Among all response-evaluable patients in Part A, 3 (10%) had a partial response (PR) and 19 (63%) had stable disease (SD); In patients with ER+/HER2- breast cancer, PR was observed in 1 (10%) and SD was observed in 5 (50%); In patients with CCNE1-amplified high grade serous ovarian cancer (HGSOC)/fallopian, PR was observed in 2 (20%) and SD was observed in 8 (80%); Monotherapy safety and antitumor activity data support continued investigation of INX-315 as monotherapy in CCNE1-amplified solid tumors and in combination with standard of care therapies for ER+/HER2- breast cancer."

P1/2 data • Estrogen Receptor Positive Breast Cancer • Fallopian Tube Cancer • HER2 Negative Breast Cancer • Ovarian Cancer

Incyclix Bio Announces Clinical Trial Collaboration and Supply Agreement with Lilly to Evaluate INX-315 in Combination with Verzenio (abemaciclib) and Fulvestrant in HR+/HER2- Breast Cancer (GlobeNewswire) - "Incyclix Bio, LLC...announced a clinical trial collaboration and supply agreement with Eli Lilly and Company (Lilly) for supply of its CDK4/6 inhibitor Verzenio (abemaciclib) for use in combination with INX-315 and fulvestrant for treatment of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer who progressed on a prior CDK4/6i regimen....Under the terms of the agreement, Lilly will provide abemaciclib to Incyclix Bio, who will conduct and sponsor the combination study....Combination therapy to be evaluated as part of ongoing Phase 1/2 study in patients with HR+/HER2- metastatic breast cancer; Incyclix plans to initiate combination cohorts with INX-315 in fourth quarter of 2024."

Commercial • Trial status • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Incyclix Bio Announces Abstract Accepted for Presentation at 2024 San Antonio Breast Cancer Symposium (GlobeNewswire) - "'We look forward to sharing our progress evaluating our CDK2 inhibitor in patients with CDK4/6 inhibitor resistant ER+/HER2- breast cancer or CCNE1 amplified solid tumors at SABCS'....'This is an exciting opportunity to connect with the oncology community to discuss advancements in breast cancer and further highlight the potential of INX-315 to improve treatment for patients with advanced and resistant breast cancer'."

P1/2 data • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

A Highly Anticipated Selective Therapeutic Agent against CDK2: INX-315. (PubMed, Cancer Discov) - "This agent shows promise in CCNE1-amplified cancers and in CDK4/6 inhibitor-resistant breast cancers. See related article by Dietrich et al., p. 446 (8)."

Journal • Breast Cancer • Oncology • Solid Tumor • CCNE1 • CDK2

INX-315, a selective CDK2 inhibitor, induces cell cycle arrest and senescence in solid tumors. (PubMed, Cancer Discov) - "Using cell-based assays, patient-derived xenografts, and transgenic mouse models, we show that INX-315 (i) promotes retinoblastoma protein hypo-phosphorylation and therapy-induced senescence (TIS) in CCNE1-amplified tumors, leading to durable control of tumor growth; (ii) overcomes breast cancer resistance to CDK4/6i, restoring cell cycle control whilst re-instating the chromatin architecture of CDK4/6i-induced TIS; and (iii) delays the onset of CDK4/6i resistance in breast cancer by driving deeper suppression of E2F targets. Our results support the clinical development of selective CDK2 inhibitors."

Journal • Breast Cancer • Eye Cancer • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor • CCNE1

INX-315, a potent and selective CDK2 inhibitor, demonstrates robust antitumor activity in CCNE1-amplified cancers (AACR 2023) - "Lastly, in CCNE1-amplified xenograft models of ovarian and gastric carcinomas, INX-315 inhibited Rb-phosphorylation and induced tumor regression. These data demonstrate INX-315 to be a potent and selective CDK2 inhibitor that may benefit patients with CDK2/cyclin E driven cancers."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • CCNE1 • ER

INX-315-01: Open-Label Study to Evaluate the Safety, Tolerability, PK, and Efficacy of INX-315 in Patients With Advanced Cancer (clinicaltrials.gov) - P1/2 | N=81 | Recruiting | Sponsor: Incyclix Bio | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • CCNE1 • ER • HER-2

Incyclix Bio Announces FDA Clearance of Investigational New Drug Application for INX-315 in Patients with Advanced or Metastatic Cancer (GlobeNewswire) - "Incyclix Bio...announced that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for the Company’s lead compound, INX-315, a novel, potent and selective CDK2 inhibitor. The Phase 1/2 first-in-human study (INX-315-01) will evaluate the safety, pharmacokinetics (PK), and preliminary antitumor activity of INX-315 in patients with advanced/metastatic cancers....Incyclix expects to initiate the study during the 1st quarter of 2023."

IND • Trial initiation date • Oncology • Solid Tumor

INX-315-01: Open-Label Study to Evaluate the Safety, Tolerability, PK, and Efficacy of INX-315 in Patients With Advanced Cancer (clinicaltrials.gov) - P1/2 | N=81 | Not yet recruiting | Sponsor: Incyclix Bio

Metastases • New P1/2 trial • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • CCNE1 • ER • HER-2