CB307 / Crescendo Biologics - LARVOL DELTA

A Phase I Dose Escalation and Cohort Expansion Study of CB307, a Trispecific Humabody against PSMA, CD137, and Albumin in Patients with PSMA-Positive Solid Tumors (Clin Cancer Res) - P1 | N=70 | NCT04839991 | Sponsor: Crescendo Biologics Ltd. | "CB307 was administered to 75 patients....Durable RECIST responses were observed in two patients with metastatic castration-resistant prostate cancer enrolled in the 800 mg CB307 monotherapy and in one patient in the combination cohort (overall response rates: 11.1% and 7.1%, respectively). A disease control rate (DCR) of 50% was observed in patients enrolled in the 800 mg CB307 monotherapy cohort and 42.9% in the combination cohort. In a post hoc analysis, the response was numerically better in patients who had not received chemotherapy in the 6 months prior to starting CB307 (ORR = 20%, DCR = 60% vs. ORR = 0%, DCR = 37.5%)."

P1 data • Castration-Resistant Prostate Cancer

A phase I dose escalation and cohort expansion study of CB307, a trispecific Humabody® against PSMA, CD137, and albumin in patients with PSMA-positive solid tumors. (PubMed, Clin Cancer Res) - "This Phase I study investigated the safety and tolerability of CB307 as monotherapy or with pembrolizumab. In a post-hoc analysis, the response was numerically better in patients who had not received chemotherapy in the 6 months prior to starting CB307 (ORR = 20%, DCR 60% vs. ORR 0%, DCR 37.5%). CB307 induces cytotoxic cell expansion in tumors and PD-L1 expression."

IO biomarker • Journal • P1 data • Castration-Resistant Prostate Cancer • Hepatology • Oncology • Prostate Cancer • Solid Tumor • PD-L1 • TNFRSF9

Phase I study to assess biodistribution of CB307, a trispecific Humabody targeting CD137, prostate-specific membrane antigen, and human serum albumin with 89Zr-CB307 PET (ESMO 2024) - P1 | "CB307 targets PSMA only in tumors, without specific uptake in PSMA-positive normal tissues or lymphoid tissues."

P1 data • Trispecific • Oncology • Salivary Gland Cancer • TNFRSF9

Solving selectivity issues in LBAs: case study using Gyrolab to quantify CB307, a bispecific Humabody in human serum. (PubMed, Bioanalysis) - P1 | " Matrix effects were mitigated using strategies including increasing minimum required dilution (MRD) and lower limit of quantification, optimization of antibody orientation, assay buffer and solid phase. The strategies described resulted in a selective method for CB307 in disease state matrix that met bioanalytical method validation (BMV) guidance and is currently used to support clinical pharmacokinetic sample analysis in the first-in-human POTENTIA clinical study (NCT04839991) as a secondary clinical end point."

Journal

CB307: A dual targeting costimulatory Humabody® VH therapeutic for treating PSMA-positive tumors (AACR 2024) - "The potent CD137 agonist urelumab has shown clinical promise as a cancer immunotherapeutic but development has been hampered by on-target off-tumour toxicities. CB307 is a first-in-class immunotherapeutic that triggers potent PSMA-dependent T cell activation thereby alleviating toxicological concerns against unrestricted CD137 agonism."

Colorectal Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

CB307: A Dual Targeting Costimulatory Humabody VH Therapeutic for Treating PSMA-Positive Tumors. (PubMed, Clin Cancer Res) - "The potent CD137 agonist urelumab has shown clinical promise as a cancer immunotherapeutic but development has been hampered by on-target off-tumor toxicities. CB307 did not show substantial toxicity in nonhuman primates and exhibited a plasma half-life supporting weekly clinical administration. CB307 is a first-in-class immunotherapeutic that triggers potent PSMA-dependent T-cell activation, thereby alleviating toxicologic concerns against unrestricted CD137 agonism."

Journal • Colorectal Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Crescendo Biologics presents preclinical data on lead clinical candidate CB307 and unveils its first ‘2 in 1’ immune cell engager CB699 at AACR 2024 (GlobeNewswire) - "CB307 demonstrated effective activation of both T and NK cells via the co-stimulatory receptor CD137 in a PSMA-dependent manner. Its combination with PD-(L)1 inhibitors showed supra-additive anti-tumour activity, which is retained even in absence of tumour PD-L1 expression, potentially enabling a wider patient population to benefit from checkpoint inhibitor therapies. Although prostate cancer has been considered an ‘immunologically cold’ tumour type, the data revealed co-localisation of CD137 and PSMA in metastatic prostate cancer lesions, supporting the use of CB307 in mCRPC."

Preclinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Crescendo Biologics to present at the 2024 AACR Annual Meeting (GlobeNewswire) - "Crescendo Biologics Ltd...will be presenting two poster presentations at the 2024 American Association for Cancer Research (AACR) Annual Meeting, taking place in San Diego, California from 5-10 April 2024."

Clinical data • Oncology • Solid Tumor

CBT307-1: A Phase I Study to Assess PSMA+ and PSMA- Tumour Lesions (clinicaltrials.gov) - P1 | N=5 | Active, not recruiting | Sponsor: Crescendo Biologics Ltd. | Recruiting ➔ Active, not recruiting | N=12 ➔ 5 | Trial completion date: Dec 2023 ➔ Oct 2024

Enrollment change • Enrollment closed • Trial completion date • Oncology • Prostate Cancer • Solid Tumor

Crescendo Biologics announces first U.S. patients dosed in expanded Phase 1b clinical trial of CB307 for patients with mCRPC (GlobeNewswire) - "Crescendo Biologics Ltd...announces that the first patients in the U.S. have been dosed as part of the ongoing Phase 1b study of CB307, Crescendo’s lead programme in PSMA+ metastatic castration-resistant prostate cancer (mCRPC)."

Trial status • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Crescendo Biologics secures $32M and announces expansion of CB307 Phase 1b trial in PSMA+ solid tumours (Businesswire) - "Crescendo Biologics Ltd...announces that it plans to augment the ongoing Phase 1b clinical trial of CB307 through the addition of a new pembrolizumab (anti-PD-1) combination expansion cohort. Additional financing of $32 million has been secured with the support of all major existing shareholders, including Sofinnova Partners, Andera Partners, IP Group BioNTech, Takeda and Quan Capital, and new investor Kreos Capital to fund the additional combination expansion arm of the adaptive clinical protocol....The additional pembrolizumab combination expansion cohort is expected to be initiated in Q3 2023 and will be open to those with PSMA+ mCRPC."

Clinical protocol • Financing • Trial status • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

POTENTIA: Study of CB307 in Patients With Advanced and/or Metastatic PSMA-positive Tumours. (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: Crescendo Biologics Ltd. | Trial completion date: Sep 2023 ➔ Sep 2024 | Trial primary completion date: Jul 2023 ➔ Jul 2024

Trial completion date • Trial primary completion date • Oncology • Prostate Cancer • Solid Tumor

CB307: A Novel T-Cell Costimulatory Humabody VH Therapeutic for PSMA-Positive Tumours (PEGS 2023) - No abstract available

Oncology

POSTER HIGHLIGHT: CB307: A Novel T-Cell Costimulatory Humabody VH Therapeutic for PSMA-Positive Tumours (PEGS 2023) - P1 | "CB307 mediates CD137 reporter cell signalling in PSMA dependent manner and enhances human T cells activity in co-culture assay. The first in human clinical study (NCT04839991) is ongoing."

Oncology • TNFRSF9

A Phase I Study to Assess PSMA+ and PSMA- Tumour Lesions (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Crescendo Biologics Ltd.

New P1 trial • Oncology • Prostate Cancer • Solid Tumor

CB307: a novel targeted CD137 agonist for enhancement of immune cell responses to PSMA+ tumors (AACR 2023) - P1 | "CB307 or PD-1/PD-L1 inhibition alone induced IL-2 secretion in PBMC/PSMA-expressing tumor cell cocultures; this effect was synergistically enhanced when CB307 was combined with either PD-1 or PD-L1 inhibition. CB307 augmented tumor cell killing in 3D spheroids containing PSMA-expressing cells. Enhanced tumor cell killing was observed in spheroid cultures containing CB307 in combination with PD-1/PD-L1 inhibition."

Immune cell • IO biomarker • Bladder Cancer • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • FOLH1

Angle PLC Announces Pharma Services Contract with Crescendo Biologics (Issuer Direct) - "ANGLE plc...is delighted to announce that it has signed a contract with a new customer, Crescendo Biologics Limited ('Crescendo')....Crescendo will use ANGLE's recently launched Portrait Flex assay in its ongoing Phase 1 clinical trial (NCT04839991) investigating the safety and efficacy of CB307, Crescendo's first-in-class prostate-specific membrane antigen (PSMA) x CD137 half-life extended bispecific, for the treatment of patients with PSMA positive solid tumours....Crescendo will use the Portrait Flex assay in the cohort expansion part of its ongoing clinical study, sending patient samples to ANGLE's ISO15189 accredited clinical laboratories for processing using the Parsortix system and analysis."

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

CB307: A novel selective CD137 agonist for enhancement of immune cell responses to PSMA+ tumors (AACR 2022) - P1 | "In reporter assays and PBMC cocultures, CB307 activated CD137 only in the presence of PSMA-expressing cells leading to enhanced immune cell activation. Enzalutamide pre-treatment of 22Rv1 (PSMA-low) cells induced a 1.5-fold increase in surface PSMA expression leading to enhanced CB307 activity. CB307 or PD1/PDL1 inhibition alone induced IL-2 secretion in PBMC/PSMA-expressing tumor cell cocultures; this effect was synergistically enhanced when CB307 was combined with either PD1 or PDL1 inhibition."

IO biomarker • Bladder Cancer • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • FOLH1

A phase 1 open-label, dose escalation and expansion trial to investigate the safety, pharmacokinetics and pharmacodynamics of CB307, a Trispecific Humabody® T-cell enhancer, in patients with PSMA+ advanced and/or metastatic solid tumors (POTENTIA) (AACR 2022) - P1 | "PSMA-PET scan and tumor biopsy are taken to understand the mechanism of action of CB307 as well as a change of PSMA expression during CB307 treatment. NCT04839991 * “Humabody” is a registered trademark ® of Crescendo Biologics Ltd."

Clinical • IO biomarker • P1 data • PK/PD data • Genito-urinary Cancer • Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • CDK12 • FOLH1 • TNFRSF9

POTENTIA: Study of CB307 in Patients With Advanced and/or Metastatic PSMA-positive Tumours. (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: Crescendo Biologics Ltd. | N=50 ➔ 70

Enrollment change • Oncology • Prostate Cancer • Solid Tumor

CB307: A Novel T-Cell Costimulatory Humabody® VH Therapeutic for PSMA-Positive Tumours (PEGS 2022) - "CB307 is a novel trispecific Humabody therapeutic targeting CD137, prostate specific membrane antigen (PSMA) and human serum albumin (HSA). The molecular weight of CB307 is"

Hepatology • Oncology • TNFRSF9

CB307: A Novel T-Cell Costimulatory Humabody® VH Therapeutic for PSMA-Positive Tumours (PEGS 2022) - No abstract available

Oncology

Crescendo Biologics Announces Prestigious New Collaboration With the Institute of Cancer Research, London (Businesswire) - "Crescendo Biologics Ltd...announces a new translational science collaboration with The Institute of Cancer Research, London, one of the world’s most influential cancer research organisations. Working together, Crescendo and The Institute of Cancer Research (ICR) will further characterise the non-clinical pharmacology of CB307, Crescendo’s first-in-class lead programme...The alliance with the ICR will drive valuable mechanistic insights into the pharmacology of CB307 in both in vitro and in vivo settings."

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

[VIRTUAL] A phase I open-label, dose escalation and expansion trial to investigate the safety, pharmacokinetics and pharmacodynamics of CB307, a trispecific Humabody T-cell enhancer, in patients with PSMA+ advanced and/or metastatic solid tumors (POTENTIA) (AACR 2021) - "Patients with brain metastases, patients who have discontinued previous immunotherapy due to intolerable immune-related adverse events and patients with acute infections or autoimmune diseases are excluded from the study. * “Humabodies” is a registered trademark of Crescendo Biologics Ltd."

Clinical • IO biomarker • P1 data • PK/PD data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • CDK12

Crescendo Biologics announces initiation of Phase 1 study of CB307 in patients with advanced, PSMA-positive solid tumours (Businesswire) - "Crescendo Biologics...today announces that the first patient has entered the POTENTIA trial, a Phase 1, open-label, monotherapy study of CB307, the most advanced Humabody® in Crescendo’s portfolio of T cell enhancers....The POTENTIA trial is a Phase 1, multi-centre, non-randomised study of CB307 in patients with advanced and/or metastatic PSMA-positive solid tumours...The primary endpoint of the trial is to assess the safety and tolerability of CB307 and to determine the maximum tolerated dose."

Trial status • Oncology • Solid Tumor