On July 11, 2023 Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage biopharmaceutical company focused on developing innovative treatments for cancer, reported a collaboration with the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) to evaluate radiopharmaceutical versions of MNPR-101 in several aggressive cancers (Press release, Monopar Therapeutics, JUL 11, 2023, View Source [SID1234633165]). MNPR-101 is a novel, first-in-class humanized monoclonal antibody to the urokinase Plasminogen Activator Receptor (uPAR).

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Dr. Anand Jeyasekharan, MBBS MRCP (UK) PhD, of CSI Singapore, NUS, will be the Principal Investigator on the collaboration. Dr. Jeyasekharan is a physician-scientist who runs a research laboratory investigating the molecular and biological responses of cancer cells to oncology drugs, as well as treats cancer patients and leads early phase oncology clinical trials at NUS.

In this collaboration, Dr. Jeyasekharan will initially investigate uPAR expression levels in tissue samples from patients with various subtypes of advanced soft tissue sarcoma (ASTS). Studies have shown uPAR to be a promising target for ASTS, which is a cancer Dr. Jeyasekharan specializes in treating. He plans to assess retrospective patient samples to identify which subtypes of ASTS have the highest expression of uPAR, thus making them the most promising to pursue in a human clinical trial.

"uPAR is an exciting target for ASTS, and a radiopharmaceutical approach using MNPR-101 has the potential to combine personalized medicine with precision oncology," said Dr. Jeyasekharan. "We have the chance here to use immunohistochemistry on patient tissue samples to identify high uPAR expressing cancers, to then work with our colleagues in radiology and nuclear medicine to radiolabel MNPR-101 for a subsequent clinical imaging study. For patients with positive scans, a therapeutic isotope such as Lu-177 or Ac-225 may provide an interesting option for a clinical trial."

"It is exciting what Dr. Jeyasekharan and NUS are aiming to do here," said Chandler Robinson, MD, CEO of Monopar. "They are seeing if we can select patients most likely to respond at the time of tissue biopsy. And from there, if you can see it on PET/SPECT imaging with a radiopharmaceutical version of MNPR-101, you can treat it. Dr. Jeyasekharan is uniquely equipped to undertake this endeavor, too, as he can oversee both the preclinical work as well as the overall management of patients under standard Phase 1 protocols."

On July 11, 2023 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported that the first patient was dosed in a Sanofi-sponsored Phase 1/2 clinical trial (NCT05839626), evaluating SAR’514 / IPH6401 in relapsed/refractory Multiple Myeloma (RRMM) and Relapsed/Refractory Light-chain Amyloidosis (RRLCA) (Press release, Innate Pharma, JUL 11, 2023, View Source [SID1234633164]).

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SAR’514 is a trifunctional anti-BCMA NKp46xCD16 NK cell engager, using Sanofi’s proprietary CROSSODILE multi-functional platform, which comprises the Cross-Over-Dual-Variable-Domain (CODV) format. It induces a dual targeting of the NK activating receptors, NKp46 and CD16, for an optimized NK cell activation, based on Innate’s ANKET (Antibody-based NK cell Engager Therapeutics) proprietary platform.

The purpose of the dose escalation and dose expansion study is to evaluate the safety, pharmacokinetics and preliminary efficacy of SAR’514 in monotherapy in patients with RRMM and RRLCA.

Joyson Karakunnel, MD, MSc, FACP, Chief Medical Officer at Innate Pharma "We are pleased to see a second molecule from our ANKET platform reaching the clinic. In addition to the targeting of the tumor antigen BCMA, SAR’514 / IPH6401 co-engages the two activating receptors NKp46 and CD16 to leverage the advantages of harnessing NK cell effector functions against cancer cells and thus has the potential to be a new innovative option for patients living with Relapsed/Refractory Multiple Myeloma or Light-chain Amyloidosis."

Peter Adamson, MD, Global Development Head, Oncology, Sanofi "We are excited to see our collaboration with Innate Pharma continue to move forward, leveraging scientific advances in our understanding of the potential of NK cells to impact cancer. Our first patient dosed with SAR’514 / IPH6401 is indeed welcome news. We look forward to data as it emerges, with the goal of improving the outcome for patients with relapsed/refractory multiple myeloma (RRMM) or relapsed/refractory light-chain amyloidosis (RRLCA)."

The start of the trial has triggered a milestone payment from Sanofi to Innate, which is part of a previously announced research collaboration with Sanofi.

More information about the Phase 1/2 trial can be found on clinicaltrials.gov.

About ANKET

ANKET (Antibody-based NK cell Engager Therapeutics) is Innate’s proprietary platform for developing next-generation, multi-specific natural killer (NK) cell engagers to treat certain types of cancer.

This versatile, fit-for-purpose technology is creating an entirely new class of molecules to induce synthetic immunity against cancer.

On July 11, 2023 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809; NASDAQ: EVO) reported that Bristol Myers Squibb Company (NYSE:BMY) has exercised its option to enter into an exclusive global licence agreement (Press release, Evotec, JUL 11, 2023, View Source [SID1234633163]). The licence covers selected late-stage discovery programmes that were developed and progressed within the collaboration.

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Evotec and Bristol Myers Squibb originally entered their neurodegeneration partnership in 2016. The initial partnership proved highly productive in generating a promising pipeline of discovery to clinical-stage programmes. Based on this success, Bristol Myers Squibb and Evotec have extended and expanded the partnership for an additional 8 years in March to further broaden and deepen the strategic alliance.

Under the licence agreement, Bristol Myers Squibb has selected an undisclosed number of programmes that were rapidly developed and progressed using Evotec’s precision medicine platforms for further development within the expanded collaboration. Evotec receives a $ 40 m payment and is eligible to earn performance milestone payments, as well as tiered royalties up to low double-digit percentages on product sales.

Dr Cord Dohrmann, Chief Scientific Officer of Evotec, commented: "This licence agreement will further bolster our joint pipeline of programmes targeting several neurodegenerative conditions. We are confident that the strong collaboration of the experienced teams at Evotec and Bristol Myers Squibb will make novel innovative treatment options available to patients living with a broad range of neurodegenerative conditions."

Evotec and Bristol Myers Squibb aim to identify disease-modifying treatments for a broad range of neurodegenerative diseases. Currently approved drugs only offer short-term management of patients’ symptoms and there is a significant unmet medical need for therapies that slow down or reverse disease progression in the field of neurodegenerative diseases.

This partnership pursues an innovative approach to the discovery and development of novel medicines by leveraging several of Evotec’s modality-agnostic precision medicine platforms. The partnership has already been successful in generating a pipeline of discovery and pre-clinical-stage programmes. A first programme, BMS-986419 or EVT8683, targeting eIF2b, was in-licensed by Bristol Myers Squibb in September 2021, following the successful filing of an IND application with the FDA and has proceeded into the clinical Phase I.

On July 11, 2023 Enterome, a clinical-stage company developing first-in-class immunomodulatory drugs for cancer and immune diseases based on its unique Mimicry platform, reported that the first patient has been dosed at The University of Texas MD Anderson Cancer Center (Houston, TX) in the Phase 2 ‘CLAUDE’ trial evaluating EO2040, the Company’s fourth OncoMimics immunotherapy candidate to enter clinical development (Press release, Enterome, JUL 11, 2023, View Source [SID1234633161]). The CLAUDE trial will assess the immunogenicity and the preliminary efficacy of EO2040 in combination with nivolumab and as a monotherapy in patients with circulating tumor DNA (ctDNA) defined minimal residual disease (MRD) stage II-IV colorectal cancer (CRC) after completion of surgical resection and all other standard of care treatments.

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EO2040 is an innovative, off-the-shelf immunotherapy that combines two synthetic OncoMimics peptides. These non-self, microbial-derived peptides correspond to CD8 HLA-A2 epitopes that exhibit molecular mimicry with the tumor-associated antigens (TAAs) FOXM1 & BIRC5. EO2040 also includes universal cancer peptide 2 (UCP2), a helper peptide representing the CD4+ epitope.

The CLAUDE study (EOCRC1-22; NCT05350501) is the first trial to use liquid biopsy monitoring to measure ctDNA clearance as an indicator of OncoMimics immunotherapy efficacy. A total of 34 patients are expected to be enrolled in this multi-center, open-label Phase 2 study in the US and Europe.

Circulating tumor DNA (ctDNA) assays can reveal minimal residual disease after surgical resection of a tumor in patients who appear radiographically free of disease, by detecting and analyzing traces of tumor DNA in a blood sample. Detection of ctDNA after completion of curative-intent therapy predicts with nearly 100% specificity the risk of cancer recurrence. The lead time between ctDNA detection and radiographic evidence of cancer recurrence is up to nine months, providing a window for the evaluation of novel therapeutic strategies.

The primary objective of the CLAUDE trial is to assess the six-month ctDNA clearance rate – with ctDNA clearance being used as a surrogate endpoint for prolongation of disease-free survival (DFS). ctDNA clearance is characterized by the disappearance of all somatic mutations identified in the blood, as well as no appearance of any additional new somatic mutations, and radiographic investigations showing no evidence of CRC.

Dr Pierre Belichard, CEO of Enterome, said: "We are delighted to begin a new clinical study to evaluate the potential of our new OncoMimics immunotherapy EO2040 to treat a second colorectal cancer indication. This latest trial is particularly interesting due to its use of liquid biopsy monitoring to measure ctDNA clearance as an indicator of treatment efficacy. If CLAUDE is successful, then it could open multiple opportunities in other major cancer indications where the use of ctDNA monitoring to detect residual disease after surgery and other standard of care treatment is used. This would support Enterome’s ambition to build a significant and valuable OncoMimics franchise and provide the Company with a uniquely differentiated position and ability to deliver a broad pipeline of next-generation OncoMimics immunotherapies."

On July 11, 2023 Bristol Myers Squibb (NYSE: BMY) reported that the sub-study of the Phase 3 CheckMate -901 trial met the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR) at final analysis (Press release, Bristol-Myers Squibb, JUL 11, 2023, View Source;901-Trial/default.aspx [SID1234633160]). Results of the sub-study showed that Opdivo (nivolumab) in combination with cisplatin-based chemotherapy followed by Opdivo monotherapy demonstrated statistically significant benefits in OS and PFS compared to standard-of-care cisplatin-based combinations as a first-line treatment for patients with unresectable or metastatic urothelial carcinoma who are eligible for cisplatin-based chemotherapy. The combination of Opdivo with cisplatin-based chemotherapy in first-line urothelial carcinoma had a tolerable safety profile consistent with the known safety profiles of the individual components of the regimen. No new safety concerns have been identified.

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"Today’s news is yet another example of the power of immunotherapy combinations to transform outcomes for patients with cancer. Opdivo with cisplatin-based chemotherapy is the first immunotherapy-based combination to improve both overall survival and progression-free survivalin patients with previously untreated unresectable or metastatic urothelial carcinoma who are eligible for cisplatin-based chemotherapy, reinforcing the benefits of Opdivo-based treatments seen across a variety of genitourinary cancers, including durable survival in advanced renal cell carcinoma and a reduced risk of recurrence in resectable muscle-invasive urothelial carcinoma," said Dana Walker, M.D., M.S.C.E., vice president, global program lead, genitourinary cancers, Bristol Myers Squibb. "We are encouraged by these positive results and remain steadfast in our commitment to bringing new solutions to patients with high unmet needs. We thank the patients, investigators and all site personnel involved in the CheckMate -901 trial."

The company will complete a full evaluation of the available data and looks forward to sharing the results with the scientific community at an upcoming medical conference as well as discussing the results with health authorities.

The CheckMate -901 primary study, evaluating Opdivo plus Yervoy (ipilimumab) vs. standard-of-care cisplatin- or carboplatin-based chemotherapy in patients with untreated, unresectable or metastatic urothelial carcinoma remains ongoing. Opdivo has previously shown clinical benefit across various stages of urothelial carcinoma, including in the second-line setting of metastatic urothelial carcinoma and the adjuvant setting of muscle-invasive urothelial carcinoma for patients who are at a high risk of recurrence post-radical surgery.

In addition to resectable or metastatic urothelial carcinoma, Opdivo and Opdivo-based combinations have shown significant improvements in OS in Phase 3 clinical trials across several tumors, including advanced renal cell carcinoma, non-small cell lung cancer, malignant pleural mesothelioma, metastatic melanoma and esophageal squamous cell carcinoma.

About CheckMate -901

CheckMate -901 is a Phase 3, randomized, open-label trial evaluating Opdivo in combination with Yervoy (primary study) or Opdivo in combination with chemotherapy (sub-study) compared to standard-of-care chemotherapy alone, in patients with untreated unresectable or metastatic urothelial cancer.

In this sub-study of CheckMate -901, a total of 608 patients eligible for cisplatin-based chemotherapy were randomized to receive either Opdivo 360 mg in combination with chemotherapy every 3 weeks or chemotherapy alone. The primary endpoints of the sub-study are overall survival (OS) and progression-free survival (PFS).

The OS and PFS outcomes for patients who are eligible for cisplatin-based chemotherapy are based on the final efficacy analysis for these endpoints of the CheckMate -901 sub-study.

About Urothelial Carcinoma

Bladder cancer is the 10th most common cancer in the world, with more than 573,000 new cases diagnosed annually. Urothelial carcinoma, which most frequently begins in the cells that line the inside of the bladder, accounts for approximately 90% of bladder cancer cases. In addition to the bladder, urothelial carcinoma can occur in other parts of the urinary tract, including the ureters and renal pelvis. The majority of urothelial carcinomas are diagnosed at an early stage, but approximately 50% of patients who undergo surgery will experience disease progression and recurrence within two-to-three years post-surgery. Additionally, approximately 20% to 25% of patients with urothelial carcinoma develop metastatic disease. The poor durability of responses seen with chemotherapy alone in the first-line setting presents a major challenge in the treatment of metastatic disease, and there are limited treatment options in the second-line setting for patients with advanced urothelial carcinoma.