On June 23, 2021 Microbiotica, a leading player in microbiome-based therapeutics and biomarkers, reported that MB097 is now in pre-clinical development for treatment of patients not responding to anti-PD1 therapy (Press release, Microbiotica, JUN 23, 2021, View Source [SID1234584275]). Clinical trials are due to begin in 2022. MB097 is clinically designed and experimentally validated.

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Studies have shown that the gut microbiome plays a critical and causative role in determining which cancer patients respond to Immune Checkpoint Inhibitor (ICI) therapy. However clinical translation of this ground-breaking discovery has been hampered by large inconsistencies between studies in the intestinal bacteria associated with anti-PD1 efficacy. The Microbiotica platform is unrivalled in the comprehensiveness and precision by which it can profile the microbiome of patients. It has enabled the Company to identify the first microbiome signature predictive of response to ICI therapy across four independent melanoma studies, by analysing MELRESIST, a melanoma study conducted in collaboration with Cambridge University Hospitals. This microbiome signature is a highly predictive clinical biomarker in advanced melanoma and is also predictive in non-small cell lung cancer (NSCLC).

The bacteria most significantly linked to outcome are all elevated in patients that respond to anti-PD1 based therapy, suggesting that gut microbes drive ICI efficacy by enhancing the anti-tumour immune response. MB097 is a Live Bacterial Therapeutic (LBT) comprising nine key species from the signature, and is being developed as a co-therapy with ICI in advanced melanoma and NSCLC. MB097 has shown potent anti-tumour efficacy in a mouse syngeneic tumour model. The bacteria also demonstrate multiple immuno-stimulatory mechanisms in primary human immune cell assays, leading to Cytotoxic T Lymphocyte activation and tumour cell killing in vitro.

Clinical testing of MB097, in combination with anti-PD1, will begin in 2022 with a Phase 1b study conducted in the same melanoma patient population that the microbiome signature was derived from. This is precision medicine enabled by the precise microbiome profiling of Microbiotica’s platform.

ICIs have transformed oncology, having increased the range of cancers that can be treated as well as improving levels of efficacy, including complete remission in some cases. However, response rates tend to be low, typically in the range 10%-40% of patients. Consequently, there is a major unmet need for co-therapies to increase the number of responders and for biomarkers to stratify patients for treatment.

Mike Romanos, Co-founder and CEO, Microbiotica, said:

"Immune Checkpoint Inhibitors have had a major impact on the lives of many cancer patients, however fewer than half respond to this type of immunotherapy. This has driven us to design a microbiome therapeutic to improve patient response rate. Through our MELRESIST study data and our platform, we have been able to identify a consistent bacterial signature predictive of drug response in advanced melanoma and NSCLC.

"The Live Bacterial Therapeutic, MB097, arising from this signature, aims to tap into this predictive signature of ICI therapy response. Preclinical in vivo data and mechanistic in vitro human cell data generated thus far have been hugely encouraging. Coupled with our ongoing collaboration with Cancer Research UK and Cambridge University Hospitals, our IO program is now a significant focus for the Company going forward. The aim is for us to enter the clinic in 2022 with this programme."

Microbiotica’s platform comprises the world’s leading Reference Genome Database and Culture Collection of gut bacteria, and an unrivalled capability to culture and characterise all gut bacteria from patients at scale. This is complemented by a suite of bioinformatic and machine learning tools that enable the identification of previously undetectable gut bacterial signatures linked to patient phenotype.

On June 23, 2021 BioAffinity Technologies, a privately held biotech company, reported that it will present the Company’s discoveries in the field of cancer diagnostics and therapeutics at the RNA Therapeutics Institute’s 2021 RNA Therapeutics Symposium June 23 – 25, 2021, and the International Conference on Porphyrins and Phthalocyanines (ICPP) June 28 – July 3, 2021 (Press release, BioAffinity Technologies, JUN 23, 2021, View Source [SID1234584291]).

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"The presentation describes the novel mechanism by which the porphyrin TCPP, which is used in bioAffinity Technologies’ non-invasive test for the early detection of lung cancer, is incorporated into cancer cells"

bioAffinity Senior Vice President of Therapeutics, William Bauta, Ph.D., will present "Selective Cancer Cell Killing by Dual siRNA Knockdown of CD320 and LRP2 Receptors" on June 23 at the RNA Therapeutics Institute’s Symposium sponsored by the University of Massachusetts Medical School. Dr. Bauta will discuss how bioAffinity has successfully used RNA interference to knock down expression of two genes that results in killing cancer cells with little or no effect on normal cells. Dr. Bauta’s live presentation will be Wednesday, June 23, from 3:30 p.m. to 4:15 p.m. EDT. A video presentation by bioAffinity Vice President of Research, David Elzi, Ph.D., also will be available throughout the conference for viewing by conference participants.

"bioAffinity’s discovery of a fundamental vulnerability of cancer opens the way to new therapies that kill cancer without harm to normal tissue," Dr. Bauta said. "In particular, bioAffinity’s research shows how the Company has designed and used siRNAs to kill multiple cancers at the cellular level including prostate, lung, breast, brain and skin cancers without harm to normal cells."

"Recent scientific discoveries and their application in medicine related to RNAs has been astonishing, leading to life-saving therapies including the use of mRNA vaccines to eradicate the SARS-Cov-2 virus causing the COVID-19 pandemic," said bioAffinity President and CEO Maria Zannes. "We are honored to be part of the 2021 RNA Symposium that brings together leaders in the field to discuss what the world is witnessing – that RNA can be the future of therapeutics."

Dr. Bauta also will present the poster "Meso-tetra (4-carboMeso-tetra (4-carboxyphenyl) porphyrin (TCPP) is taken up in cancer cells by the CD320 receptor" at the International Conference on Porphyrins and Phthalocyanines (ICPP) ICPP-11 from June 28 through July 3.

"The presentation describes the novel mechanism by which the porphyrin TCPP, which is used in bioAffinity Technologies’ non-invasive test for the early detection of lung cancer, is incorporated into cancer cells," Ms. Zannes said. "Our discoveries have furthered the understanding of TCPP for use in diagnostics, including the Company’s first product, CyPath Lung, a flow cytometry test used to diagnose lung cancer at early stage."

A test validation trial comparing people at high risk for lung cancer to patients with the disease resulted in CyPath Lung sensitivity of 92% and specificity of 87% for individuals with nodules less than 20 mm.

Precision Pathology Services, a CAP/CLIA laboratory in San Antonio, Texas, is completing validation of CyPath Lung as a Laboratory Developed Test for sale to physicians who will order the test for their patients suspected of having lung cancer. Patients collect a sputum sample non-invasively at home and ship the sample overnight to the laboratory where it is analyzed for cell types and populations indicating a tumor in the lung.

"CyPath Lung is a well-balanced, highly accurate test allowing patients to collect their sample in the privacy of their own home," Ms. Zannes said. "Precision Pathology’s commercial validation of the test is going very well and expected to be complete this summer."

On June 23, 2021 Novartis reported that VISION data published in The New England Journal of Medicine (NEJM) shows that 177Lu-PSMA-617 plus standard of care (SOC) significantly improved both overall survival (HR = 0.62 [95% CI: 0.52−0.74]; P<0.001; median 15.3 vs 11.3 months) and imaging-based progression-free survival (HR = 0.40 [99.2% CI: 0.29−0.57]; P<0.001; median, 8.7 vs 3.4 months) versus SOC alone in patients with progressive PSMA-positive mCRPC1 (Press release, Novartis, JUN 23, 2021, View Source [SID1234584276]). VISION data were first presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 6 (see media release).

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"We are proud of these data showing that 177Lu-PSMA-617 can significantly shrink tumors and extend life for patients with prostate cancer, who have been heavily pre-treated and currently have limited treatment options," said Jeff Legos, Global Head of Oncology Development, Novartis. "We believe that radioligand therapy with 177Lu-PSMA-617 has great potential to improve outcomes in advanced prostate cancer and have already started two new Phase III studies in earlier lines of treatment."

Other data highlighted in the publication and ASCO (Free ASCO Whitepaper) presentation:

Median time to first symptomatic skeletal event or death was 11.5 months in the 177Lu-PSMA-617 plus SOC arm versus 6.8 months in the SOC only arm (P<0.001; α=0.05; HR = 0.50 [95% CI: 0.40, 0.62])1
Overall response rate in patients with measurable or non-measurable disease at baseline was 29.8% partial or complete response in the 177Lu-PSMA-617 plus SOC arm compared to 1.7% partial response in the SOC only arm (two-sided p-value: <0.001)1
The incidence of grade ≥3 treatment-emergent adverse effects was 52.7% in the 177Lu-PSMA-617 plus SOC arm vs 38.0% in the SOC only arm1
Serious drug-related treatment emergent adverse events occurred in 9.3% of patients in the 177Lu-PSMA-617 plus SOC arm compared to 2.4% in the SOC only arm2
Two additional studies with 177Lu-PSMA-617 radioligand therapy in earlier lines of treatment for metastatic prostate cancer are ongoing, investigating potential clinical utility in the mCRPC pre-taxane setting (PSMAfore) and in the metastatic hormone-sensitive setting (PSMAddition). Novartis is also evaluating opportunities to investigate 177Lu-PSMA-617 radioligand therapy in earlier stages of prostate cancer.

The NEJM publication is available online at www.NEJM.org

About 177Lu-PSMA-617
177Lu-PSMA-617 is an investigational PSMA-targeted radioligand therapy for metastatic castration-resistant prostate cancer. It is a type of precision cancer treatment combining a targeting compound (ligand) with a therapeutic radioisotope (a radioactive particle)3-5. After administration into the bloodstream, 177Lu-PSMA-617 binds to prostate cancer cells that express PSMA6, a transmembrane protein, with high tumor-to-normal tissue uptake3,7,8. Once bound, emissions from the radioisotope damage tumor cells, disrupting their ability to replicate and/or triggering cell death9-11. The radiation from the radioisotope works over very short distances to limit damage to surrounding cells1,3,7.

About VISION
VISION is an international, prospective, randomized, open-label, multicenter, phase III study to assess the efficacy and safety of 177Lu-PSMA-617 (7.4 GBq administered by intravenous infusion every 6 weeks for a maximum of 6 cycles) plus investigator-chosen standard of care in the investigational arm, versus standard of care in the control arm1. Patients with PSMA PET-scan positive mCRPC, and progression after prior taxane and androgen receptor pathway inhibitors, were randomized in a 2:1 ratio in favor of the investigational arm1. The alternate primary endpoints were rPFS and OS1. The study enrolled 831 patients1.

On June 23, 2021 Arcus Biosciences, Inc. (NYSE:RCUS), an oncology-focused biopharmaceutical company working to create best-in-class cancer therapies, reported that, at the first interim analysis of the three-arm randomized Phase 2 ARC-7 study, both arms with domvanalimab-based combinations showed encouraging clinical activity (measured by overall response rate; ORR) when given as an initial treatment (first-line) to people with metastatic, PD-L1≥50% non-small cell lung cancer (NSCLC) (Press release, Arcus Biosciences, JUN 23, 2021, View Source [SID1234584292]). The zimberelimab monotherapy arm showed activity similar to that of marketed anti-PD-1 antibodies studied by other companies in this setting. At the time of data cut off, no unexpected safety signals were observed; and the current safety profile for each arm of the study appears to be consistent with known immune checkpoint inhibitors in this setting. All three arms of the ARC-7 trial, and the ongoing ARC-10 Phase 3 registrational study, will continue to enroll as planned; and ARC-7 data will be submitted later this year for presentation at a medical conference."

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Our partner Gilead Sciences has an exclusive option to co-develop and co-commercialize domvanalimab and is anticipated to make a decision regarding opting into the anti-TIGIT program later this year. Arcus and Gilead will continue preparations for additional Phase 3 studies of domvanalimab-based combinations and explore development plans for combinations including domvanalimab and etrumadenant.

"This analysis of the dataset for the ongoing ARC-7 study revealed encouraging clinical activity for the anti-TIGIT domvanalimab-based combinations, and furthermore, that the anti-PD-1 zimberelimab monotherapy arm showed activity similar to that of marketed anti-PD-1 antibodies studied in this setting," said Bill Grossman, M.D., Ph.D., Chief Medical Officer of Arcus. "Next steps are to complete enrollment in all our open domvanalimab studies, execute on our broader plans for Phase 3 studies for domvanalimab across multiple cancer types, and further explore combinations with domvanalimab and etrumadenant."

Conference call details

Arcus will host a conference call and live webcast today, Wednesday, June 23, 2021 at 2:00 p.m. Pacific Time/5:00 p.m. Eastern Time to provide an update on its ongoing domvanalimab program. Investors interested in listening to the conference call may do so by dialing (877) 209-6698 in the U.S. or (825) 312-2373 internationally, using Conference ID: 6891607. In addition, the live webcast and accompanying slides will be available on the "Investors" section of the Arcus website at www.arcusbio.com. Following the live webcast, a replay will be available on the Company’s website for approximately 30 days.

About ARC-7 and the domvanalimab Development Program

ARC-7 is an open-label randomized Phase II study evaluating the safety and efficacy of domvanalimab plus zimberelimab (anti-PD1 antibody) vs. zimberelimab alone vs. domvanalimab plus zimberelimab and etrumadenant (dual adenosine A2a/A2b receptor antagonist) in 150 people as a first-line treatment for PD-L1 ≥ 50% and EGFR/ALK wild-type, metastatic NSCLC. Participants are being randomized 1:1:1 across three study arms and treated until disease progression or loss of clinical benefit. Co-primary endpoints are objective response rate (ORR) and progression-free survival (PFS). Secondary endpoints include safety, duration of response and disease control rates. In this first interim analysis, data were not mature, and PFS was not assessed.

In addition to ARC-7, domvanalimab is currently being evaluated in ARC-10, an ongoing registrational Phase 3 study evaluating domvanalimab plus zimberelimab vs. zimberelimab alone vs. chemotherapy in first-line locally advanced or metastatic, PD-L1>50% NSCLC. Based on the ARC-7 data, additional Phase 3 studies are planned for domvanalimab-based combination across various cancer types.

About domvanalimab and Arcus’ anti-TIGIT program

Domvanalimab, Arcus’ most advanced anti-TIGIT candidate, is an Fc-silent investigational monoclonal antibody that binds to TIGIT, a protein receptor on immune cells that acts as a brake on the immune response. Cancer cells can exploit TIGIT to avoid detection by the immune system. Domvanalimab binds to TIGIT to free up immune activating pathways and activate immune cells to attack and kill cancer cells.

Arcus is developing a second anti-TIGIT candidate, AB308, an Fc-enabled investigational monoclonal antibody in clinical development, with a potential focus on hematological malignancies. AB308 is currently in Phase I studies for advanced malignancies.

On June 16, 2021, Ocuphire Pharma, Inc. ("Ocuphire") reported that entered into a License Agreement (the "License Agreement") with Processa Pharmaceuticals, Inc. ("Processa"), pursuant to which Ocuphire granted Processa an exclusive license to develop, manufacture and commercialize RX-3117 globally, excluding China (Filing, 8-K, Rexahn, JUN 16, 2021, View Source [SID1234584277]).

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As consideration for the License Agreement, Ocuphire will receive 44,689 shares of Processa common stock and a $200,000 cash payment. As additional consideration, Processa will pay Ocuphire development and regulatory milestone payments upon the achievement of certain milestones, which primarily consist of dosing a patient in pivotal trials or having a drug indication approved by a regulatory authority in the United States or another country. In addition, Processa must pay Ocuphire one-time sales milestone payments based on the achievement during a calendar year of one or more thresholds for annual sales for products made and pay royalties based on annual licensing sales. Processa is also required to give 32% of any milestone payments received to Ocuphire based on any sub-license agreement it may enter into with respect to the Licensing Agreement.

Processa is required to use commercially reasonable efforts, at its sole cost and expense to oversee such commercialization efforts, to research, develop and commercialize products in one or more countries, including meeting specific diligence milestones that consist of: (i) first patient administered drug in a clinical trial of a licensed product prior to the three (3) year anniversary of the effective date; and (ii) first patient administered drug in a pivotal clinical trial of a licensed product or first patient administered drug in a clinical trial for a second indication of a licensed product prior to the five (5) year anniversary of the effective date. Either party may terminate the agreement in the event of a material breach of the agreement that has not been cured following written notice and a 120-day opportunity to cure such breach, and Processa may terminate the agreement for any reason upon 120 days prior written notice to Ocuphire.