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First patient treated in Clarity’s Cu-64 SAR-bisPSMA prostate cancer trial

On August 10, 2021 Clarity Pharmaceuticals, a clinical stage radiopharmaceutical company focused on the treatment of serious disease, reported that the first patient has been dosed in the 64Cu SAR-bisPSMA clinical trial in patients with confirmed prostate cancer (Press release, Clarity Pharmaceuticals, AUG 10, 2021, View Source [SID1234586179]).

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Clarity’s Executive Chairman, Dr Alan Taylor, commented, "We are very excited to have treated our first patient in this clinical trial for men with confirmed prostate cancer using our optimised PSMA agent, 64Cu SAR-bisPSMA, at GenesisCare CTA Medical Clinic in Perth, Australia. We look forward to recruiting additional patients at all three of the clinical sites and generating data to confirm the compelling results from our preclinical studies."

SAR-bisPSMA derives its name from the word "bis", which reflects the novel approach of connecting two PSMA binding motifs to Clarity’s SAR chelator technology (instead of one) to increase tumour uptake and retention in cancerous tissues. Preclinical data confirms that both uptake and retention are higher for 64Cu SAR-bisPSMA than that of the single PSMA binding motif utilised by other radiopharmaceutical products on the market.

The PROPELLER trial is a Phase I Positron Emission Tomography (PET) imaging trial of participants with confirmed prostate cancer using 64Cu SAR-bisPSMA. It is a 30-patient multi-centre, blinded review, dose ranging, non-randomised study of 64Cu-SAR-bisPSMA administered to patients with confirmed prostate cancer prior to radical prostatectomy (NCT04839367)1. The aim of the PROPELLER trial is to determine the safety and tolerability of 64Cu SAR-bisPSMA in participants with untreated, confirmed prostate cancer and planned for radical prostatectomy, as well as compare 64Cu SAR-bisPSMA to 68Ga PSMA-11, the standard of care for prostate cancer imaging in Australia.

Dr Taylor said: "We look forward to further exploring the benefits of the Targeted Copper Theranostics (TCT) platform for patients with prostate cancer, one of the largest indications in oncology. With our 64/67Cu SAR-bisPSMA theranostic trial having commenced last week in the US (SECuRE trial (NCT04868604)2), we believe that Clarity is well positioned to leverage the logistical, manufacturing and treatment benefits associated with the optimised SAR-bisPSMA product and the "perfect pairing" of copper-64 and copper-67 to provide a large patient population with early, accurate and precise detection of prostate cancer and improve patient outcomes. These two trials, PROPELLER and SECuRE, will enable Clarity to get closer to achieving its ultimate goal of improving the treatment of children and adults with cancer."

Aravive Announces First Patient Dosed in Phase 1b/2 Clinical Trial of AVB-500 for the Treatment of Pancreatic Adenocarcinoma

On August 9, 2021 Aravive Inc. (Nasdaq: ARAV), a clinical-stage oncology company developing innovative therapeutics to treat life-threatening diseases, reported the Company has dosed the first patient in the Phase 1b portion of its Phase 1b/2 trial of AVB-500 in combination with gemcitabine and nab-paclitaxel as a first-line treatment in patients with advanced or metastatic pancreatic adenocarcinoma (Press release, Aravive, AUG 9, 2021, View Source [SID1234594062]). The Phase 1b portion of the clinical trial will evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of AVB-500 in combination with gemcitabine and nab-paclitaxel.

"We are pleased with the quick advancement of AVB-500 with the first patient dosed in our Phase 1b/2 pancreatic adenocarcinoma trial. This clinical trial addresses a very high unmet medical need in one of the most difficult-to-treat cancers with a high mortality rate," said Gail McIntyre, Ph.D., DABT, Chief Executive Officer of Aravive. "We continue to expand the development of AVB-500, as the Company now has three ongoing clinical trials of AVB-500. In addition to the pancreatic adenocarcinoma clinical trial, AVB-500 is currently being investigated in a Phase 3 clinical trial for platinum resistant ovarian cancer and a Phase 1b/2 clinical trial for clear cell renal cell carcinoma."

The Phase 1b/2 clinical trial is designed to evaluate AVB-500 as a first-line therapy in combination with gemcitabine and nab-paclitaxel (Abraxane) in patients with advanced or metastatic pancreatic adenocarcinoma eligible to receive gemcitabine and nab-paclitaxel combination therapy. The Phase 1b portion of the clinical trial will evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity in approximately 20 patients dosed with 15 mg/kg of AVB-500 in combination with gemcitabine and nab-paclitaxel. The randomized, controlled Phase 2 portion of the clinical trial is designed to evaluate approximately 60 patients dosed with 15 mg/kg of AVB-500 as a first-line therapy in combination with gemcitabine and nab-paclitaxel versus gemcitabine and nab-paclitaxel alone. The primary endpoint of the Phase 2 portion of the trial is progression-free survival. The secondary endpoints are objective response rate, duration of response, clinical benefit rate, safety and overall survival, and the exploratory endpoints are pharmacokinetics and pharmacodynamics. The Phase 1b/2 trial is listed on clinicaltrials.gov NCT04983407.

About Pancreatic Cancer
Pancreatic cancer is the seventh leading cause of cancer death worldwide. There were approximately 495,800 new cases of pancreatic cancer and 466,000 deaths from the disease worldwide in 2020. It is estimated that there will be approximately 60,400 new cases of pancreatic cancer and 48,200 deaths from the disease in the U.S. in 2021. Pancreatic cancer typically has a poor prognosis, and the five-year survival rate is approximately 11%. Pancreatic adenocarcinoma is the most common type of pancreatic cancer, and there is a clear, high, unmet medical need to improve patient survival with new effective treatments that are safe and well-tolerated. Pancreatic cancer is projected to become the third leading cause of cancer death worldwide by 2025 and the second leading cause of cancer death in the U.S. by 2030.

About AVB-500
AVB-500 is a therapeutic recombinant fusion protein that has been shown to neutralize GAS6 activity by binding to GAS6 with very high affinity in preclinical models. In doing so, AVB-500 selectively inhibits the GAS6-AXL signaling pathway, which is upregulated in multiple cancer types including ovarian, renal and pancreatic cancer. In preclinical studies, GAS6-AXL inhibition has shown anti-tumor activity in combination with a variety of anticancer therapies, including radiation therapy, immuno-oncology agents, and chemotherapeutic drugs that affect DNA replication and repair. Increased expression of AXL and GAS6 in tumors has been correlated with poor prognosis and decreased survival and has been implicated in therapeutic resistance to conventional chemotherapeutics and targeted therapies. AVB-500 is currently being evaluated in multiple clinical trials and has been granted Fast Track Designation by the U.S. Food and Drug Administration in platinum resistant recurrent ovarian cancer. Analysis of all safety data to date showed that AVB-500 has been generally well tolerated with no dose-limiting toxicities or unexpected safety signals.

First Patient Dosed in Phase 1b/2 AML Trial at Chaim Sheba Medical Center Israel

On August 9, 2021 Race Oncology Limited ("Race") reported that the first patient has been dosed in the Phase 1b/2 trial in relapsed/refractory Acute Myeloid Leukaemia (ASX Announcement: 22 June 2021) (Press release, Race Oncology, AUG 9, 2021, View Source [SID1234591494]).

This investigator-led trial supervised by Professor Arnon Nagler will use Zantrene (bisantrene dihydrochloride) in a novel three drug combination which has demonstrated compelling efficacy in pre-clinical studies (ASX Announcement: 10 May 2021). Prof Nagler was the Principal Investigator of the Phase 2 investigator-initiated trial where Zantrene was used as a single agent in R/R AML patients and reported an impressive 40% clinical response rate (ASX Announcement: 16 June 2020).

"We are delighted to see the start of this important clinical project which uses a novel combination approach for relapsed or refractory Acute Myeloid Leukaemia. This study is also an important step in our journey towards approval of Zantrene in this area of high unmet medical need."

Race CMO Dr David Fuller
The trial will run in parallel with a separate Australian Phase 2 trial in patients with extramedullary AML (ASX Announcement: 2 June 2021).

Both trials are key components of Race’s Three Pillar strategy.

Even when CR is achieved through intense chemotherapy, approximately half of the younger and 80% of the older patients, relapse. In both clinical situations, refractory and/or relapsed AML, active disease remains a major therapeutic challenge despite recent advances in the clinic.

"This study led by Professor Nagler who has good experience with Zantrene, supports the building of additional data in AML in line with our Three pillar strategy plan. We hope to see improved patient outcomes in what has been historically a difficult to treat disease. We plan on using our trademarked name, Zantrene, in referring to bisantrene dihydrochloride. It’s one of our registered trademarks and its protection is enhanced by its ongoing and appropriate use."

Race CEO & MD Phillip Lynch
Relapsed or Refractory Acute Myeloid Leukemia
Primary refractory or relapsed Acute Myeloid Leukemia is associated with poor prognosis and remains a serious therapeutic challenge. Primary refractory AML is defined by the absence of complete remission (CR), manifested by blast count of ≥5% in bone marrow after one or two cycles of intense induction chemotherapy.

Up to 30% of adults with newly diagnosed AML fail to achieve CR after two courses of intensive chemotherapy.

Clinical Trial Design
The trial is an open-label, Phase 1b/2 study of intravenous FluCloZan (Fludarabine, Clofarabine, Zantrene) in cohorts of up to 12 adult patients with R/R AML with a Phase 1b dose escalation stage to establish the maximum tolerated dose (MTD) or recommended Phase 2 dose of the combined FluCloZan regimen, followed by a Phase 2 expansion stage to determine efficacy and confirm safety of FluCloZan at the recommended Phase 2 dose in up to 17 patients.

Phase 1b, Dose-Escalation (Lead-in Stage)
A two-cohort dose escalation schema using a standard 3 + 3 design will be employed.

Cohort 1 will enroll three patients to receive the FluCloZan regimen for four consecutive days. If no dose limiting toxicities (DLTs) have occurred in the first three patients by day 30 of their first cycle of treatment, then Cohort 2 will receive the treatment for five days (with the extra day representing dose escalation).

Phase 2, Expansion (Efficacy Stage)
Up to 17 patients will be enrolled into a Phase 2 expansion efficacy cohort using a 2-stage Simon design. Initially, 9 patients will be enrolled and treated with the recommended Phase 2 dose of FluCloZan as determined in the Phase 1b part of the study. If there are no patient responses in the first nine subjects according to the response criteria outlined in the European Leukemia Net (ELN) guidelines, the study will be terminated for futility. If at least one patient shows a response, eight more patients will be enrolled and treated. If three or more of the patients treated in Stage 2 respond, the null hypothesis of treatment futility can be rejected.

Efficacy assessments will be based on bone marrow examination at a minimum of two time points on Day 21 and on Day 30. A further bone marrow examination may be performed on Day 42 at the investigator’s discretion, based on patient’s disease and performance status and/or on peripheral blood hematology results during the treatment course and between Day 21 to 42.

Treatment will be terminated upon any sign of progressive/recurrent disease and/or referral to pre-transplant conditioning therapy for (allogeneic) stem cell transplantation.

Patients who do not progress or experience any DLTs may receive a second course of treatment for the same duration as in their first cycle.

All patients will be actively followed-up every three months for a further 12 months following completion treatment for disease free survival (DFS) and overall survival (OS).

Indicative Costs and Timelines
The trial is expected to take 36 to 40 months to complete with full patient recruitment over approximately 18 months. Given the trial is open-label, Race expects that data will be reported at interim points throughout the trial.

Race will pay Chaim Sheba a total fee of USD $668,739 over the study’s life. Payments will be made to Chaim Sheba upon reaching key milestones and the total trial cost will depend on the number of patients recruited and other operational variables.

Clinical Trial Summary
Study Title An Open-label, Phase Ib/II, Two-stage, Study of Zantrene (Bisantrene) in combination with Fludarabine and Clofarabine as Salvage Therapy for Adult Patients with Relapsed or Refractory Acute Myeloid Leukaemia (AML)
Registration NCT04989335
Phase of Development Phase 1b/2
Active Ingredient Bisantrene dihydrochloride, Fludarabine, Clofarabine (FluCloZan)
Study Description Phase 1b/2 study of FluCloZan, IV, in cohorts of adult patients with R/R AML using a 2-stage design: a Phase 1b lead-in dose escalation stage to establish the MTD or RP2D of FluCloZan and a Phase 2 expansion stage to determine efficacy and confirm safety of the FluCloZan regimen at the RP2D.
Principal Investigator Professor Arnon Nagler
Sponsor Race Oncology
Indication/population Adult men and women 18 to 65 years of age with relapsed and/ or refractory Acute Myeloid Leukemia (R/R AML) presenting with non-CNS extramedullary disease.
Number of Subjects Phase 1b: up to 12 patients Phase 2: up to 17 patients in the expansion phase
Study Period 36 – 40 months
Study Design A two-cohort dose escalation schema using a standard 3 + 3 design will be employed followed by an expansion phase at the RP2D. As the patient population is considered relapsed and/or refractory to existing treatments, a comparator arm will not be used.
Statistical methods Simon 2 stage design
End Points Primary
Phase 1b Dose Escalation: number of subjects experiencing a DLT in each cohort Phase 2 Expansion: Overall Response Rate (ORR) defined as the proportion of subjects with CR and CRi between Day 30 to Day 42 Secondary: Transplant/allo-HSCT rates (for transplant/allo-HSCT-eligible subjects); Combined CR and CRi and PR response rate; Morphologic leukemia-free state (MLFS); Partial remission (PR); Stable disease (SD); Progressive disease (PD); Relapse; Disease free survival (DFS); Overall survival (OS); Time to next treatment (for transplant/allo-HSCT-ineligible subjects)
Participating Centres 1 Chaim Sheba Medical Center, Tel Hashomer, Israel
Dates First patient August 6, 2021; Last patient (anticipated): Q3 CY2023

Sareum Holdings plc (“Sareum” or the “Company”) Subscription to raise £1,000,000 to progress proprietary TYK2/JAK1 programmes into clinical development

On August 9, 2021 Sareum Holdings plc (AIM: SAR), the specialist drug development company, reported that it has raised £1,000,000, before expenses, through a subscription by a high net worth individual (the "Subscriber") for 12,121,212 new ordinary shares of 0.025p each in the capital of the Company ("Ordinary Shares") (the "Subscription Shares") at a price of 8.25p per share (the "Subscription Price") (the "Subscription") (Press release, Sareum, AUG 9, 2021, View Source [SID1234586711]).

Under the terms of the Subscription, the new Subscriber will also be issued one and a quarter five-year warrants, exercisable at the Subscription Price, for every Subscription Share issued (the "Subscription Warrants"), which can only be exercised following the Company’s closing middle market share price being above 10.25p per Ordinary Share for five consecutive days. The Subscription Price represents a discount of approximately 6.8 per cent. to the closing middle market price for Sareum shares on 6 August 2021.

The net proceeds from the Subscription will be used to progress the Company’s SDC-1801 and SDC-1802 TYK2/JAK1 inhibitor drug development programmes as well as for working capital purposes. As noted in the Company’s Trading Update of 25 May 2021, the Company is targeting the filing of a Clinical Trials Approval for SDC-1801 in Q4 2021, subject to successful progress and no further delays with the final preclinical studies. Clinical trial plans, including priority autoimmune indications and potential Covid-19 application, will also be developed in parallel, subject to additional funding being raised.

Application will be made for the 12,121,212 Subscription Shares, which will rank pari passu with the Company’s existing Ordinary Shares, to be admitted to trading on the AIM market of the London Stock Exchange ("AIM") ("Admission"). It is anticipated that Admission will become effective at 8.00 am on 17 August 2021. The Subscription is subject to normal conditions including, inter alia, Admission.

Total Voting Rights

For the purpose of the Disclosure Guidance and Transparency Rules, following the above issue of equity, the issued share capital of the Company will comprise 3,365,701,148 Ordinary Shares. The above figure may be used by shareholders as the denominator for the calculations by which they will determine if they are required to notify their interest in, or a change to their interest in, the Company, under the Disclosure Guidance and Transparency Rules.

Dr Tim Mitchell, CEO of Sareum Holdings plc, said: "This new subscription is Sareum’s fourth since 1 June this year, reflecting the strong and continuing interest in our proprietary TYK2/JAK1 development programmes in autoimmune diseases, including the immune overreaction to Covid-19, and cancer. With the funds raised during this period now totalling over £4.5 million, our financial position has been significantly strengthened and we are looking forward to completing the preclinical studies with SDC-1801 and advancing it into clinical development, and to progressing the preclinical development of our second TYK2/JAK1 inhibitor SDC-1802."

The information contained within this announcement is deemed by the Company to constitute inside information as stipulated under the Market Abuse Regulation (EU) No. 596/2014 as it forms part of United Kingdom domestic law by virtue of the European Union (Withdrawal) Act 2018.

QIAGEN and OncXerna Therapeutics sign licensing and master companion diagnostic agreements

On August 9, 2021 QIAGEN (NYSE:QGEN; Frankfurt Prime Standard: QIA) and OncXerna Therapeutics, Inc. ("OncXerna"), a precision medicine company using an innovative RNA-expression based biomarker platform to predict patient responses to its targeted oncology therapeutic candidates, reported signing a master companion diagnostics (CDx) agreement to develop a NGS CDx for OncXerna’s product candidate, Navicixizumab, and a non-exclusive license to the Xerna TME panel (Press release, Qiagen, AUG 9, 2021, View Source [SID1234586597]).

QIAGEN and OncXerna have agreed to collaborate to advance the Xerna TME panel towards IVD (in-vitro diagnostic) regulatory approval as a NGS companion diagnostic for Navicixizumab, which is being developed by OncXerna as a treatment for patients with ovarian cancer. The diagnostic will be used to determine if patients with ovarian cancer whose dominant tumor biology is driven by angiogenesis are more likely to benefit from treatment with Navicixizumab.

The Xerna TME panel uses proprietary RNA-based gene expression data and a machine learning-based algorithm to classify patients based on the dominant biology of their cancer so that patients can be matched with therapies that directly address these biologies. Pursuant to the non-exclusive license, which is for research use only ("RUO") and clinical development programs, OncXerna has granted QIAGEN the rights to integrate the Xerna TME panel into their NGS workflow solutions, which broadens QIAGEN’s NGS CDx custom panel development capabilities.

"We are very pleased to complete these agreements with QIAGEN, which we see as providing important external validation for the Xerna TME panel and our broader RNA-based biomarker platform," stated Dr. Laura Benjamin, OncXerna Founder and CEO. "As an NGS industry-leader in precision medicine diagnostics with impressive global development, manufacturing and commercial capabilities, we believe QIAGEN is uniquely positioned to help advance the Xerna TME panel towards regulatory approval as an NGS companion diagnostic and, if approved, drive the panel’s adoption. Moreover, integration of the Xerna TME Panel into their workflow solutions could enable QIAGEN to provide a new RNA-based offering to strengthen their overall immune oncology solutions for biopharma customers."

"We believe that the Xerna TME panel that we can now offer our customers will further enhance our strong portfolio in companion diagnostics. Through this agreement, we aim to foster additional NGS-based collaborations with pharmaceutical companies for the development of drug treatments for immune oncology and promote early clinical adoption of precision medicine diagnostics such as our therascreen portfolio and the Xerna TME panel," said Jonathan Arnold, Vice President, Head of Oncology and Precision Diagnostics at QIAGEN. "We are also thrilled to have the master CDx agreement in place and look forward to working with OncXerna to develop an NGS companion diagnostic for Navicixizumab based on our extensive track record with the development of companion diagnostics for a variety of cancers."

QIAGEN is a pioneer in Precision Medicine and the global leader in collaborations with pharmaceutical and biotechnology companies to co-develop companion diagnostics, which detect clinically relevant genetic abnormalities to provide insights that guide clinical decision-making in diseases such as cancer. QIAGEN has an unmatched depth and breadth of technologies from next-generation sequencing (NGS) to polymerase chain reaction (PCR) for companion diagnostic development. QIAGEN has ten PCR based companion diagnostic indications that are FDA approved, including therascreen EGFR for non-small cell lung cancer, therascreen KRAS for colorectal cancer, therascreen FGFR for urothelial cancer, therascreen PIK3CA for breast cancer based on tissue or plasma samples and the therascreen BRAF kit for colorectal cancer.

Currently, QIAGEN is working under master collaboration agreements with more than 25 companies to develop and commercialize companion diagnostic tests for their drug candidates – a deep pipeline of potential future products to advance Precision Medicine for the benefit of patients.

About OncXerna Therapeutics, its Xerna RNA-based Biomarker Platform, and Xerna TME Panel

OncXerna is a precision medicine company using an innovative RNA-expression based biomarker platform to predict patient responses to its targeted oncology therapeutic candidates. OncXerna is working to expand next-generation precision medicine to a larger group of cancer patients by leveraging the company’s Xerna platform to prospectively identify patients based on the dominant biology of their cancer. OncXerna’s approach pairs those patients with OncXerna’s clinical-stage therapeutic candidates and known mechanism of action that directly address these biologies, with the goal to substantially improve patient outcomes. The Xerna TME Panel uses proprietary RNA-based gene expression data and a machine learning-based algorithm to classify patients based on the interplay between angiogenic and immunogenic dominant biologies of the tumor microenvironment (TME), and has been developed as a clinical assay. The Xerna TME Panel is an investigational assay that has not been approved, and has not been demonstrated to be safe or effective for any use.

About Navicixizumab

Navicixizumab is an anti-DLL4/VEGF bispecific antibody product candidate that demonstrated antitumor activity in patients who were previously treated with Avastin (bevacizumab) in a Phase 1b clinical trial. The U.S. Food and Drug Administration granted Fast Track designation to navicixizumab for the treatment of high-grade ovarian, primary peritoneal, or fallopian tube cancer in patients who have received at least three prior therapies and/or prior treatment with Avastin. Navicixizumab is an investigational agent that has not been approved, and it has not been demonstrated to be safe or effective for any use, including for the treatment of advanced ovarian cancer.