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SOUTH SAN FRANCISCO, Calif.--( BUSINESS WIRE )--Circle Pharma, a clinical-stage biopharmaceutical company dedicated to discovering and developing a new generation of macrocycle therapies, today announced a poster for preclinical data on CID-078, a first-in-class oral macrocycle cyclin A/B RxL inhibitor, will be presented at the San Antonio Breast Cancer Symposium 2024. The event, which runs from December 10-13, brings together global leaders in breast cancer research and treatment. Poster presentation details are below: Author: Molina et al Title: CID-078, a first-in-class oral cyclin A/B-RxL inhibitor, elicits anti-tumor activity in breast cancer patient-derived xenograft models Poster Number: P2-05-29 Date and Time: December 11, 2024, from 5:30-7:00 PM CST The digital poster can be viewed here. The pre-clinical data showed CID-078 demonstrated single agent antitumor activity with CID-078 in preclinical models of triple-negative breast cancer (TNBC) and estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer following CDK4/6 inhibitor (CDK4/6i) therapy. In vivo activity was correlated with E2F1 and separase (ESPL1) expression and consistent with the proposed mechanism of action. Further, treatment with CID-078 increased phosphorylation of separase in sensitive breast cancer patient-derived xenograft (PDX) models. These findings suggest that CID-078 may offer a novel treatment option for patients with Triple Negative Breast Cancer or patients with ER+/HER2- breast cancer following CDK4/6i therapy. Circle Pharma is evaluating CID-078 in a multi-center Phase 1 clinical trial ( NCT06577987 ), which aims to assess safety, tolerability, and preliminary efficacy in patients with advanced cancers, including TNBC and ER+/HER2- breast cancer. About CID-078, Circle Pharma’s Cyclin A/B RxL Inhibitor Program CID-078 is an orally bioavailable macrocycle with dual cyclin A and B RxL inhibitory activity that selectively targets tumor cells with oncogenic alterations that cause cell cycle dysregulation. In biochemical and cellular studies, Circle Pharma’s cyclin A/B RxL inhibitors have been shown to potently and selectively disrupt the protein-to-protein interaction between cyclins A and B and their key substrates and modulators, including E2F (a substrate of cyclin A) and Myt1 (a modulator of cyclin B). Preclinical studies have demonstrated the ability of these cyclin A/B RxL inhibitors to cause single-agent tumor regressions in multiple in vivo models. A multi-center phase 1 clinical trial ( NCT06577987 ) is currently enrolling patients. About Circle Pharma, Inc. South San Francisco-based Circle Pharma is advancing the discovery and development of intrinsically cell-permeable macrocycles that can be delivered by multiple routes, including oral administration. Circle Pharma’s MXMO™ platform combines structure-based rational drug design and advanced synthetic chemistry to develop a new generation of macrocycle therapies for challenging targets to address unmet clinical needs. Circle Pharma is focusing its development efforts on cyclins, which are master regulators of the machinery that controls the progression of cells through the cell cycle and are key drivers in many cancers. To learn more about Circle Pharma, please visit www.circlepharma.com .

CG Oncology says its immunotherapy candidate that could help patients avoid surgery may deliver lasting responses in a certain form of bladder cancer based on late-stage trial data. The California biotech’s oncolytic virus therapy, named cretostimogene grenadenorepvec, has not yet reached median duration of response in a Phase 3 study in people with high-risk non-muscle invasive bladder cancer (NMIBC) who are unresponsive to the Bacillus Calmette-Guérin vaccine, which is usually part of a first-line regimen. That said, the median DOR exceeded 27 months at the Sept. 30 data cutoff, according to data presented Thursday at the Society of Urologic Oncology annual meeting in Dallas. For context, Merck’s Keytruda, which is often used in the second line, has a median DOR of around 16 months, CG Oncology CEO Arthur Kuan told Endpoints News in an interview. CG also reported that 97.3% of patients did not progress to muscle-invasive disease at 12 months. Also, just over half of the enrolled patients remained responsive to treatment at 24 months or more based on Kaplan-Meier estimations. Thursday’s durability data add to an interim readout in May that showed the asset cleared tumors in 75% of the 112 patients in the trial. The latest safety results were also consistent with the May data, with no reports of grade 3 or higher adverse events or treatment-related discontinuation. The most common side effects included bladder spasm, frequent urination and urgent urination. Cretostimogene “basically spares normal cells” because they don’t harbor RB/E2F1 mutations, Kuan said. Cretostimogene has the potential to become a “backbone bladder-sparing therapeutic” if it secures US approval, CG’s chief operating officer Ambaw Bellete said in a company release. Most patients in the Phase 3 did not have surgery to remove all or part of their bladder before joining the study. The biotech plans to file the treatment with the FDA in the second half of 2025. CG went public via a $380 million upsized listing on the Nasdaq in January. The company plans to launch cretostimogene alone in most markets, although it has a partnership with Kissei Pharmaceutical for Japan, South Korea, Taiwan and a number of other Asian countries except China. It had $540.7 million in cash and equivalents at the end of September, which should support it through 2027. Elsewhere, the biotech is also testing the treatment in the Phase 3 PIVOT-006 trial in intermediate-risk NMIBC. Market competition for NMIBC is steadily growing after the FDA greenlit ImmunityBio’s Anktiva plus BCG for a subgroup of patients in April. Johnson & Johnson is advancing a drug-device combination that it calls the “pretzel” for people with high- and intermediate-risk NMIBC.

Impressive response results for CG Oncology’s oncolytic immunotherapy in a late-stage bladder cancer study lend credence as to how the biotech was able to execute one of the sector’s few successful public debuts this year. The company raised $380 million in an upsized offering in January, one of the biggest biotech IPOs since 2018, and the year’s largest so far. CG Oncology is also one of the few firms to be trading up from its debut price. For more analysis, see Vital Signs: Taking the temperature on a cooling IPO cycle.High response rateThe data, presented Friday at the American Urological Association (AUA) conference, are from the single-arm Phase III BOND-003 trial in patients with high-risk non-muscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guérin (BCG) therapy. CG Oncology’s oncolytic virus, cretostimogene grenadenorepvec, led to an any-time complete response (CR) rate of 75.2% in 105 measurable patients, the study’s primary endpoint.  Of the 79 patients with a CR, none had to undergo bladder removal or showed nodal or metastatic progression, and 29 of these participants maintained the response for a year or longer. Median duration of response has not yet been reached. CG Oncology reported no Grade 3 or higher treatment-related adverse events (TRAEs) or deaths, while two patients had Grade 2 TRAEs associated with the oncolytic immunotherapy. About 62.5% of patients experienced a TRAE, with the most common being bladder spasm, pollakiuria, dysuria, micturition urgency, and haematuria.The results are important, CG Oncology chief executive Arthur Kuan told FirstWord, because many patients who fail on BCG have no other options except surgical removal of the bladder. Furthermore, because of a shortage of BCG – the standard-of-care treatment – it is currently not available to NMIBC patients with intermediate risk, or even to some high-risk patients.“There is a great need for a local, well-tolerated, and effective bladder-preserving option for patients with intermediate-risk as well as high-risk BCG-unresponsive NMIBC,” Kuan said. He added that CG Oncology will share by year-end when it expects to submit a regulatory application to the FDA for the treatment candidate.Shooting for firstWith no FDA-approved oncolytic viruses, cretostimogene stands to be a first-in-class immunotherapy. The treatment is designed to preferentially replicate in retinoblastoma (Rb) gene pathway-defective cells and trigger an anti-tumour immune response. It also features two modifications intended to boost its selectivity and potency. First, an E2F-1 promoter is added to act as a safety mechanism so the virus selectively replicates within and lyses Rb-defective tumour cells, avoiding healthy cells.Next, the gene for granulocyte-macrophage colony-stimulating factor (GM-CSF) is inserted. The cytokine is known to stimulate longer-term anti-tumour activity, and Kaun explained that “its addition to the viral construct may both prime the immune system and induce tumour-specific immunity.”