On February 14, 2023 Clarity Pharmaceuticals (ASX: CU6) ("Clarity"), a clinical-stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported favourable imaging data from its Phase I diagnostic trial of 64Cu SAR-bisPSMA in prostate cancer, PROPELLER (NCT 048393671)1. This follows the announcement of top line data in December 2022 (Press release, Clarity Pharmaceuticals, FEB 14, 2023, View Source [SID1234627155]).

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This data is currently being presented via a poster at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (GU) Symposium in San Francisco. The poster will be available on Clarity’s website once released at ASCO (Free ASCO Whitepaper) GU.

The PROPELLER trial evaluated 30 patients with confirmed prostate cancer prior to undergoing radical prostatectomy (surgical removal of the prostate) and lymph node dissection (removal). In addition to the primary (safety, tolerability, imaging efficacy) and secondary (determining the optimal dose for subsequent investigation) endpoints, the study also compared the diagnostic properties of Clarity’s 64Cu SAR-bisPSMA product to 68Ga PSMA-11, an approved standard-of-care (SOC) product for prostate cancer imaging in Australia and the US, as an exploratory objective.

The comparison evaluated prostate cancer detection and the intensity of product uptake within the same lesions (the higher the uptake, the brighter and more visible the lesion appears on the scan). The uptake of the products was measured by maximum Standardised Uptake Values (SUVmax) on the PET scans. Importantly, all scans were evaluated by two independent, blinded, central readers.

Clarity’s Executive Chairman, Dr Alan Taylor, commented, "64Cu SAR-bisPSMA detected prostate cancer lesions that are more defined and brighter on the scans than the current SOC product, 68Ga PSMA-11. This may enable detection of smaller lesions that would have otherwise gone undetected. Arming clinicians with more accurate diagnostic information helps them determine the best course of treatment for their patients and may sometimes make the difference between the removal of the prostate, a severe and life-changing surgery, and other options that may be more effective in treating the patient’s cancer while enabling better quality of life post treatment. This patient-centric approach, reinforced by the flexibility in the timing of the scan, centralised product manufacture and its broad distribution to any imaging centre with a PET camera, would be a true paradigm shift in the management of prostate cancer. We are continuing to work diligently towards the start of the diagnostic Phase III trial of SAR-bisPSMA in the US in order to make this product available to the patients who need it most."

Prof Louise Emmett, (St Vincent’s Hospital Sydney), Principal Investigator in the PROPELLER trial, commented, "It is very encouraging to see such positive imaging results from 64Cu SAR-bisPSMA, an agent we are very pleased to work with. The higher SUVmax was consistent across both independent, blinded, central readers, and, importantly, as shown on the images on the poster, 64Cu SAR-bisPSMA was able to detect disease outside of the primary lesion that was not detected with 68Ga PSMA-11. This is a very important result when it comes to patient management, and we are looking forward to further exploring these findings as we aim to better understand the benefits of 64Cu SAR-bisPSMA during the Phase III trial. With the high uptake of the product in tumours as well as the additional benefits of later imaging timepoints, we will continue to be involved in SAR-bisPSMA trials with the ultimate purpose of improving outcomes for our patients."

Results
64Cu SAR-bisPSMA was shown to be safe and well tolerated across all patients, with only 1 patient in 30 reporting a metallic taste that was mild in nature (Grade 1).

A dose of 200 MBq was determined to be the optimal dose compared to other dose levels. All trials with 64Cu SAR-bisPSMA, both currently and in the future, will be undertaken at this dose level.

64Cu SAR-bisPSMA reported higher SUVmax values compared to 68Ga PSMA-11 in the 200 MBq dose cohort (n=18), according to both readers. Images from two patients comparing the 64Cu SAR-bisPSMA and 68Ga PSMA-11 scans are depicted below in Figure 1.

In this cohort, Reader 1 was able to detect primary prostate cancer in 100% of patients when 64Cu SAR-bisPSMA was used, while 68Ga PSMA-11 showed the cancer in 77.8% of patients. Similarly, Reader 2 detected primary prostate cancer in 85.7% of patients using 64Cu SAR-bisPSMA and in 83.3% of patients when using 68Ga PSMA-11.

In one patient, secondary disease was detected by 64Cu SAR-bisPSMA in a pelvic lymph node that was not detected by 68Ga PSMA-11 (see Figure 2). The lymph node was subsequently determined to be positive for prostate cancer by histopathology.

On November 22, 2022 AmunBio, Inc., an early, pre-clinical stage biotechnology company focused on developing and commercializing novel engineered immunotherapeutic oncolytic viruses, reported a presentation, on Tuesday, December 6, 2022, at the 45th annual San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Tx., of the pre-clinical study results of AMUN-003, an investigational, first-in-class, immuno-oncologic adenovirus being developed for the treatment of multiple solid tumors, including aggressive, metastasized, triple-negative breast cancer (TNBC) (Press release, Amunbio, FEB 14, 2023, View Source [SID1234627147]).

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The development of oncolytic viral therapies, which represents a unique therapeutic paradigm within Immuno-Oncology, promises a new approach for the treatment of human cancers. AmunBio has developed a proprietary platform technology that has the potential to generate a strong pipeline of patient-centric next-generation engineered immunotherapeutic oncolytic viruses for the treatment of cancer, including triple-negative breast cancer (TNBC) and hematological malignancies.

"I believe that AmunBio’s platform technology will result in a fundamental shift of the treatment of human cancers, augmenting existing and novel treatment modalities, compared to what is possible today," said V.K. Gadi, MD, Ph.D., Deputy Director of University of Illinois Cancer Center, and a lead scientific advisor to AmunBio.

"Inside their microenvironment, many advanced solid cancers, including TNBC are hostile to the immune system and greatly minimize the effectiveness of immunotherapy. AMUN-003 is an advanced generation oncolytic adenovirus that selectively enters cancer cells followed by viral reproduction and destruction of the cancer cell on exit," Gadi added.

"During cellular infection, AMUN-003 has been engineered to produce two proteins that stimulate the immune response (GM-CSF) and sequesters an inhibitor of the immune response (TGF-b). Our data, which will be presented at SABCS this year, shows that in a highly aggressive TNBC model AMUN-003 demonstrates single agent safety and efficacy. Moreover, in the same TNBC model, combination therapy with immune Checkpoint Inhibitors synergizes with the AMUN-003, resulting in significant inhibition of further metastatic spread. Additional pre-clinical studies are underway to advance this technology into clinical trials," Gadi concluded.

Presentation details

Poster ID: PD2-03
Poster Title: Targeting TGF-b and over-expressing GM-CSF in the Tumor Microenvironment (TME) with AMUN-003 Inhibits Tumor Growth and Metastases and Augments Immune Checkpoint Inhibitor (ICI) Response in triple-negative breast cancer (TNBC)
Date/Time: December 6, 2022, 5:00 PM – 6:15 PM CST
The San Antonio Breast Cancer Symposium (SABCS), which takes place December 6-10, 2022, in San Antonio, Tx, is the premier conference for basic, translational, and clinical cancer research professionals and provides state-of-the-art information on the experimental biology, etiology, prevention, diagnosis, and therapy of breast cancer and pre-malignant breast disease.

About Breast Cancer

Breast cancer remains the most common diagnosed cancer in women and the second most common cancer overall. [1][2][3] Over 2.3 million new cases and 685,000 deaths from breast cancer occurred in 2020 and experts predict that by 2040 the burden of breast cancer will increase to over 3 million new cases and 1 million deaths every year because of population growth and aging alone.[4]

About Triple-negative Breast Cancer (TNBC)

Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, accounts for approximately 15% of all cases of breast cancers diagnosed worldwide. This subtype of breast cancer is associated with poor prognosis, as defined by low a five-year survival and high recurrence rates after adjuvant therapy. [5] TNBC, which lacks expression of the estrogen receptor (ER) and progesterone receptor (PR) and has only limited or no human epidermal growth factor receptor 2 (HER2) expression, is, unlike other subtypes of breast cancer (i.e., ER+, HER2+), more commonly diagnosed in women younger than 40 years, and disproportionately affects black women. [6] Because TNBC is not sensitive to endocrine therapy or HER2 treatment, effective standard treatment options are extremely limited. Since there are no approved targeted treatments available for the TNBC today, there is an urgent medical need to develop new treatment strategies. [7]

About AMUN-003

AMUN-003 is an investigational, first-in-class, Immuno-Oncologic adenovirus being developed for the treatment of multiple solid tumors, including aggressive, metastasized, triple-negative breast cancer (TNBC), melanoma, and other solid tumors. AMUN-003 blocks suppression of the immune response inside the tumor, stimulates the recruitment of cancer-killing immune cells and avoids non-specific inflammation. Preclinical studies with AMUN-003 in breast cancer alone, compared to prior oncolytic virus constructs, have demonstrated near-complete breast cancer inhibition. Furthermore, in preclinical studies, a single dose of AMUN-003 delayed the progression of TNBC, while a single dose of the investigational drug, in combination with Checkpoint Inhibitors, demonstrated significant inhibition of subcutaneous tumor growth and a more durable anti-cancer response. Based on these preclinical findings, treatment with AMUN-003 may lead to long-term protection from cancer recurrence. Following a planned Investigational New Drug (IND) application, which is expected in early 2023, AmunBio is planning multiple Phase 1 clinical trials of AMUN-003, alone or in combination with Checkpoint Inhibitors, in triple-negative breast cancer (TNBC), Melanoma, Non-Small Cell Lung Cancer (NSCLC), Bladder cancer and Head & Neck Cancer, to start in late 2023/early 2024.

On February 13, 2023 Odimma Therapeutics (Strasbourg, France), a biopharmaceutical company developing an innovative immunotherapy platform dedicated to the treatment of cancer and myNEO (Ghent, Belgium), a data-driven neoantigen discovery company, reported that they are expanding their existing collaboration into a clinical trial collaboration agreement (Press release, myNEO Therapeutics , FEB 13, 2023, View Source [SID1234640210]). The agreement combines Odimma’s synthetic DNA vaccine technology with myNEO’s data analysis platform for fast and accurate per-patient identification and selection of neoantigen targets predicted to elicit strong immune responses. The agreement covers a phase I and phase II clinical trial in solid tumors.

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After combining Odimma’s DNA vaccine technology with neoantigens identified by myNEO and achieving promising preclinical results in mice last year, both companies decided to continue the successful collaboration into a clinical-stage program. myNEO will utilize its proprietary, best-in-class machine learning algorithms to screen the mutational profile of individual patients to investigate personalized highly immunogenic neoantigens. For this, myNEO will explore the complete genomic profile of the tumor to find more and novel sets of highly immunogenic neoantigenic sources.

"We strongly believe that the accurate prediction of immunodominant neoantigens along with the potency of the immunization platform are the two key drivers for the success of personalized immunotherapy," said Dr Jean-Marc Limacher, Chairman of the board and co-founder of Odimma. "We are very confident that the Artificial Intelligence solution developed by myNEO will give each patient the best chances of response to immunotherapy."

Odimma will manufacture the vaccine for each patient individually using its ODI-2001 candidate. The synthetic DNA vector vaccine will encode for up to 20 patient-specific tumor neoantigens, selected by myNEO, aiming to induce a potent and precise immune response against the patient’s unique tumor. The proven enhanced efficacy results in mice – compared to other vaccines targeting the same neoantigen – together with the rapid manufacturing process Odimma has developed, highlight the potential of the technology in a personalized setting.

"The myNEO project team is excited to have Odimma as our newest partner, and to be able to enter the field of DNA cancer vaccines," said Cedric Bogaert, Chief Executive Officer and co-founder of myNEO. "We are fully convinced that a more patient-centric approach of evaluating and targeting the tumor will be an essential part of the future, and different parallel revolutions have enabled to incorporate it in a cost-efficient and logistically feasible process. The Odimma technology provides an innovative new avenue to bring the breakthroughs of personalized tumor targeting models to the patients."

The clinical phase I aims to test the personalized synthetic DNA vaccine as monotherapy in solid tumors and will be conducted in France. The trial is expected to be initiated in Q4 2023 to primarily assess feasibility and safety but also to collect early signs of efficacy. A program of translational research is closely associated to this first clinical trial.

On February 13, 2023 LegoChem Biosciences reported a license agreement with Elthera AG, a biotechnology company in Switzerland, to develop and commercialize a novel antibody-drug conjugate (ADC) therapy using a monoclonal antibody developed by Elthera (Press release, LegoChem Biosciences, FEB 13, 2023, View Source [SID1234638675]).

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The licensed asset is a monoclonal antibody with a target expressed in a variety of solid tumors including pancreatic, ovarian, breast, lung, and colorectal cancer. Under the terms of the agreement, LegoChemBio will be responsible for the future development and commercialization of any products incorporating this antibody.

Elthera will receive an upfront payment and is eligible to receive progress-dependent development and regulatory milestone payments as well as cumulative commercial milestone payments. Elthera will additionally receive royalties on net product sales.

"We are very pleased to enter into this license agreement with LegoChemBio, a global ADC company with industry-leading ADC technology," said Anne Schmidt, CEO of Elthera. "This agreement is the result of a fruitful collaboration with LegoChemBio, demonstrating the outstanding quality and therapeutic potential of our antibody. The combination with LegoChemBio’s ConjuAll technology generates a well-differentiated first-in class ADC with a wide therapeutic window that has the potential to provide new treatment options for a large number of solid tumors."

"We are pleased to enter this agreement with Elthera as we continue to expand our toolbox to maximize the value of our ADC platform. We look forward to bringing this innovative ADC drug into the clinic as LCB’s fifth ADC," said Dr. Yong-Zu Kim, CEO of LegoChemBio.

On February 13, 2023 MacroGenics Inc, a biopharmaceutical company focused on developing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported preliminary safety and anti-tumor activity data from the dose expansion phase of the Company’s ongoing Phase 1 clinical trial of lorigerlimab, a bispecific, tetravalent PD-1 × CTLA-4 DART molecule (Press release, MacroGenics, FEB 13, 2023, View Source [SID1234636050]). This investigational molecule was designed to block PD-1 with enhanced CTLA-4 blockade on dual PD-1/CTLA-4-expressing cells, such as tumor-infiltrating lymphocytes (TILs), while maintaining maximal PD-1 blockade on all PD-1-expressing cells. The preliminary data is being presented in a poster titled "Lorigerlimab, a Bispecific PD-1 × CTLA-4 DART Molecule in Patients with Metastatic Castration-Resistant Prostate Cancer: A Phase 1 Expansion Cohort" (Poster #155) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (ASCO-GU) Cancers Symposium taking place February 16-18, 2023, in San Francisco, CA.

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Cohort Expansion Results Update

The ASCO (Free ASCO Whitepaper)-GU abstract included data as of September 10, 2022; updated data as of a December 12, 2022 cut-off are included below and will be presented at ASCO (Free ASCO Whitepaper)-GU.

As of the December 12, 2022 data cut-off, 118 patients with mCRPC, melanoma, non-small cell lung cancer or microsatellite-stable colorectal cancer were enrolled in the cohort expansion phase of the lorigerlimab Phase 1 study at the dose of 6.0 mg/kg, administered intravenously every three weeks (Q3W). Confirmed objective responses were observed across the histology-specific cohorts; preliminary efficacy results for mCRPC are presented in the poster and below.

Preliminary Safety Results

The safety analysis is based on 127 patients who received lorigerlimab at a dose of 6 mg/kg Q3W, including 118 enrolled in the four dose expansion cohorts plus nine patients from dose escalation. Median exposure was 14.4 weeks (range: 1.9 – 100.1 weeks) with a median of four infusions administered per patient. Twenty-four patients remained on lorigerlimab as of the December 12, 2022 data cut-off; 103 discontinued for the following reasons: progressive disease (PD) (n=66), adverse events (AE) (n=31), patient/physician decision (n=5), or death due to PD (n=1).

The results demonstrated a manageable overall safety profile. Treatment-related AEs (TRAEs) occurred in 86.6% of patients, with the most common among them (≥15%) being fatigue, rash, pruritus, hypothyroidism, and pyrexia. Rates of grade ≥3 TRAEs and immune-related AEs were 34.6% and 7.9%, respectively. AEs resulted in treatment discontinuation in 24.4% of patients. There were no fatal AEs related to lorigerlimab.

Preliminary Anti-tumor Activity in mCRPC Cohort

As of the December 12, 2022 data cut-off, 42 patients had been enrolled in the mCRPC expansion cohort. Patients had previously received a median of two prior therapies (range: 1 – 9) for advanced disease, with 35 patients (83.3%) having received docetaxel and 34 patients (81.0%) having received androgen receptor antagonist therapy. The median exposure to lorigerlimab was 19.2 weeks (range: 3.3 – 55.1 weeks), with a median of five infusions administered per patient.

A total of 35 patients with mCRPC had measurable soft tissue disease per RECIST v1.1 at study entry. Nine of the 35 patients (25.7%) achieved confirmed partial responses (cPR). The median duration of response for these nine patients was 4.6 months (range: 2.8 – 8.6+ months), with four patients remaining on lorigerlimab as of data cut-off. Among the other five patients who had achieved cPR, four discontinued due to unrelated adverse events, and one patient discontinued due to physician decision.

Reductions in PSA levels of ≥ 50% were observed in 12 of 42 patients (28.6%), and 9 of the 12 maintained PSA50 response ≥ 3 months. Nine of 42 patients (21.4%), including the nine who achieved cPR, had reductions in their PSA levels of ≥ 90% as of the data cut-off.

"To date, checkpoint inhibition has not fared well in the treatment of patients with late-stage mCRPC. Previously, anti-CTLA-4 therapy, whether alone or in combination with an anti-PD-1 agent, resulted in increased risk for immune-related toxicity with very modest anti-tumor activity," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "We designed lorigerlimab to have preferential blockade on dual PD-1/CTLA-4-expressing cells such as TILs, which are most abundant in the tumor microenvironment. As part of this study, biomarker analyses indicated that lorigerlimab was shown to induce T-cell activation as evidenced by an increased frequency of circulating Ki67+ and ICOS+ T cells. We believe we are seeing the benefit of lorigerlimab’s design and are very encouraged by this latest data set from our ongoing Phase 1 study. Looking forward, we plan to initiate a Phase 2 study of lorigerlimab in patients with mCRPC later this year and anticipate providing an update on the proposed study later this quarter."

ASCO-GU Poster Presentation

MacroGenics’ lorigerlimab poster presentation will be available for on-demand viewing on the ASCO (Free ASCO Whitepaper)-GU website and on the "Events & Presentations" page on MacroGenics’ website at View Source

About Lorigerlimab

Lorigerlimab (previously known as MGD019) is an investigational, bispecific IgG4-based, Fc-bearing DART molecule that was designed to enhance blockade on PD-1 and CTLA-4 dual-expressing, tumor-infiltrating lymphocytes, while maintaining maximal PD-1 blockade on all circulating PD-1-expressing cells. In addition to the study described above and presented in the poster, MacroGenics is also evaluating the activity of lorigerlimab in combination with vobramitamab duocarmazine (previously known as MGC018, an investigational B7-H3-directed antibody-drug conjugate) in a study in patients with advanced solid tumors.