On May 4, 2021 ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, reported the launch of the preclinical development of its liquid tumor pipeline with the publication of results from its Phase 1 study evaluating AnktivaÔ (N-803), its IL-15 superagonist, in combination with RituxanÒ (rituximab), an anti-CD20 monoclonal antibody therapy, in patients with indolent non-Hodgkin lymphoma (iNHL), who had relapsed or were refractory after two lines of therapy (Press release, ImmunityBio, MAY 4, 2021, https://immunitybio.com/immunitybio-announces-78-percent-complete-response-following-chemotherapy-free-combination-of-il-15-superagonist-anktiva-with-rituxan-in-relapsed-non-hodgkin-lymphoma-patients/ [SID1234579039]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The peer-reviewed article titled "Phase 1 trial of N-803, an IL-15 receptor agonist, with rituximab in patients with indolent non-Hodgkin lymphoma" (see link HERE) published in the American Association for Cancer Research (AACR) (Free AACR Whitepaper) journal Clinical Cancer Research, highlights safety, efficacy, and translational data from the Company’s ongoing open-label, multi-center, dose-escalation Phase 1 study (NCT02384954).

The study was designed to evaluate Anktiva in combination with rituximab in patients with iNHL, to explore the potential of Anktiva to enhance tumor-targeting of anti-CD20 therapeutic antibodies, and to determine the safety and efficacy of subcutaneous (SQ) versus intravenous (IV) administration. Anktiva has been engineered to exhibit a longer half-life and more potent trans-presentation relative to endogenous IL-15 to promote natural killer (NK) cell and T cell expansion to control cancer.

Key study results include:

The combination regimen of Anktiva and Rituxan was well tolerated with a single reported grade 4 adverse event (AEs) and no reported grade 5 AEs
For patients with anti-CD20 mAb sensitive disease, the overall response rate (ORR) in the SQ cohort was 78% (7 of 9)
7 of 7 (100%) responses in the SQ cohorts were complete remissions (CR)
Prolonged stable disease (SD) and conversion of SD and/or partial response (PR) to CRs with a prolonged duration without progression were observed, with 8 of 12 patients without progression at 18-24 months
For the 5 patients with anti-CD20 mAb refractory disease in both IV and SQ cohorts, the ORR was 2 of 5 (40%) with 1 CR, 1 PR, 1 SD, and 2 progressive disease (PD) with the PR and SD are ongoing at over 18 months
In correlative immunology experiments, Anktiva in combination with Rituxan induced the expansion, activation and modulation of NK cells and CD8+ T cells, with minimal impact on CD4+ T cells and Tregs
Multi-dimensional mass cytometry studies demonstrated remodeling of iNHL patient immune landscapes by promotion of an activation signature in nearly all main immune cell lineages including NK cells, CD8+ TEM, gd T cells, and CD14 and CD16 monocytes
Todd Fehniger, M.D., Ph.D, Washington University School of Medicine in St Louis, said, "These encouraging data suggest that Anktiva, ImmunityBio’s IL-15 superagonist, has the potential to enhance the activity of an anti-CD20 therapeutic antibody. We believe the excellent safety profile seen in the SQ cohort, when combined with compelling efficacy which includes prolonged progression free survival and a 78% complete response rate in rituximab-sensitive patients, warrants the further exploration of this regimen in iNHL patients. The translational immunology data generated also provide important proof-of-mechanism, with activation of important cell population including NK Cells and CD8+ T cells, which are key in driving immunotherapy responses. Together, these results suggest Anktiva may have broad potential to enhance the activity of therapeutic monoclonal antibodies across a wide range of tumor types."

The study enrolled patients with iNHL (follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, lymphoplasmacytic lymphoma) that were relapsed or refractory after >2 prior lines of therapy. Patients were considered anti-CD20 mAb refractory if they progressed on anti-CD20 mAb therapy within 6 months of their last dose of anti-CD20 mAb. Treatment consisted of IV rituximab 375 mg/m2 and IV or SQ N-803 (in increasing dosing cohorts of 1, 3, 6, 10, 15, 20 µg/kg).

On May 4, 2021 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) and the University Hospital Erlangen reported a partnership regarding molecular analyses of biospecimens from the German Chronic Kidney Disease ("GCKD") cohort study (Press release, Evotec, MAY 4, 2021, View Source;announcements/press-releases/p/evotec-and-the-gckd-study-enter-into-strategic-collaboration-to-build-a-unique-molecular-patient-database-6059 [SID1234579038]). Under the agreement, the research team will make use of Evotec’s proprietary EVOpanOmics and EVOpanHunter platforms to facilitate deep molecular profiling of patient samples. The Evotec platforms combine enhanced throughput proteomics, high-throughput transcriptomics and integrated data analysis.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Initiated in 2009, GCKD was designed to be the world’s largest cohort study on chronic kidney disease. Scientists from eleven universities work together with more than 150 practicing nephrologists to monitor more than 5,000 patients with CKD with biospecimens being taken and supporting interviews being conducted multiple times during the interval. Evotec will also financially support GCKD, which will enable the extension of this important cohort study beyond the initial term of 10 years, allowing future follow-up visits and additional sample analysis.

The multi-omics analysis of the biospecimens from the GCKD cohort study is expected to lead to a deeper understanding of different kidney disease etiologies, their respective disease mechanisms, progression and potential complications. Together with Evotec’s existing molecular patient database, this systematic integrated exploitation of the GCKD biobank will open the door to novel starting points for drug discovery and the identification of biomarkers, enabling precision medicine approaches for highly effective treatment options for clearly defined patient populations.

Dr Cord Dohrmann, Chief Scientific Officer of Evotec, commented: "We continue to work towards our goal to build a highly comprehensive molecular patient database. This collaboration is a major step forward towards this goal and we are very excited about the opportunity to work with this unique network. The GCKD cohort not only complements and expands our already leading kidney disease data base with well-documented long-term survey of CKD patients and corresponding patient samples. The more comprehensive the data base, the more impactful it will be in re-defining patient populations according to disease mechanisms rather than symptoms, identify suitable molecular targets for intervention and stratify patient populations for clinical trials."

Prof. Dr Kai-Uwe Eckardt, Director of the Department of Nephrology and Medical Intensive Care at the Charité – Universitätsmedizin Berlin, and Principal Investigator of the GCKD Study, said: "CKD is a severe health problem that affects 10% of the population. The underlying mechanisms are complex and strong efforts are urgently needed to better understand this complexity. We are very excited to enter this collaboration with Evotec, which creates novel synergies and provides the prospect for innovative diagnostic and therapeutic approaches that can be translated into patient care."

Prof. Dr Anna Köttgen, Head of the Institute of Genetic Epidemiology at the University of Freiburg, and Member of the GCKD Steering Committee added: "We are looking forward to expand the spectrum of molecular analyses in this cohort, which will greatly facilitate the discovery of robust associations between complex molecular phenotypes and clinical outcomes."

"One of the challenges in studying CKD is the gradual decline of kidney function that may eventually lead to kidney failure. The GCKD study is unique as a long-term observational study and its extension will further increase the value of this huge research project," added Prof. Dr Mario Schiffer, Director of the Department of Nephrology and Hypertension at the Friedrich-Alexander-Universität Erlangen-Nürnberg, and also Member of the GCKD Steering Committee.

On May 4, 2021 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) reported that it will announce its financial results for the first quarter of 2021 on Tuesday, 11 May 2021 (Press release, Evotec, MAY 4, 2021, View Source;announcements/press-releases/p/evotec-se-to-announce-results-for-the-first-quarter-2021-on-11-may-2021-6061 [SID1234579037]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Company is going to hold a conference call to discuss the results as well as to provide an update on its performance. The conference call will be held in English.

Conference call details

Date: Tuesday, 11 May 2021

Time: 02.00 pm CET (08.00 am EST, 01.00 pm GMT)

On May 4, 2021 Clarity Pharmaceuticals, a clinical stage radiopharmaceutical company focused on the treatment of serious disease, reported that it has received a response from the U.S. Food and Drug Administration (FDA) on its Investigational New Drug (IND) application that the study for selection and treatment of Prostate-Specific Membrane Antigen (PSMA) positive prostate cancers using 64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA may proceed (Press release, Clarity Pharmaceuticals, MAY 4, 2021, View Source [SID1234579036]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The SECuRE trial (Systemic Cu theranostics in prostate cancer) is a Phase I/IIa study for identification and treatment of PSMA-expressing metastatic castrate resistant prostate cancer (mCRPC), which will be conducted in the U.S. (NCT04868604)1. It is a theranostic multi-centre, single arm, dose escalation study with a cohort expansion planned for up to 44 patients. The trial employs diagnostic Positron Emission Tomography imaging with 64Cu-SAR-bisPSMA for selection of patients suitable for therapy cycles with 67Cu-SAR-bis-PSMA.

Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of death worldwide2. The American Cancer Society estimates in 2021 there will be 248,530 new cases of prostate cancer in the U.S. and around 34,130 deaths from the disease3. For metastatic prostate cancer, the 5-year relative survival rate is 30%, indicating a high unmet need for early detection and better treatment options for mCRPC. Annually, there are around ~34,000 men in the U.S. who are diagnosed with mCRCP3, ~90% of whom have tumours which express PSMA4.

Although there are some new therapeutic radiopharmaceutical agents for prostate cancer in late phase clinical trials, given the large patient population, product supply for therapeutic radiopharmaceuticals presents a constraint as they rely on the production of therapeutic isotopes from a small number of nuclear reactors, with reactor shutdowns often causing isotope shortages around the globe.

Clarity’s SAR-bisPSMA product utilises two isotopes of copper, which do not have the same constraints:

The therapeutic product utilises copper-67, which is being produced domestically in the USA on electron accelerators, avoiding the issues commonly associated with the production of isotopes on nuclear reactors.
The diagnostic product utilises copper-64, which is regularly produced in significant volumes on cyclotrons in the U.S., and has a half-life of 12.7 hours, avoiding the short half-life issues of other diagnostic isotopes.
The diagnostic and therapeutic products can be centrally manufactured and shipped as finished product direct to the treatment centres, which removes the need for dedicated radiopharmacy facilities at treatment centres.
Dr Alan Taylor, Clarity’s Executive Chairman, commented on the IND approval, "The FDA response suggests not only the importance of developing novel treatments for men with late-stage prostate cancer, whose prognosis is currently very poor, but also validates Clarity’s copper pairing paradigm and the centralised manufacturing concept, which differentiates it from the competitor products and enables product supply to the levels suitable for use in large patient indications."

"We are very excited to commence the SECuRE trial in mCRCP patients and have engaged a world class group of key opinion leaders in the prostate cancer space to support the development of 64/67Cu SAR-bisPSMA. Clarity’s Global Clinical Development Group has unrivalled experience in the commercialisation of the only currently approved radiotherapeutic for prostate cancer. The FDA response is a crucial milestone in the development of SAR-bisPSMA theranostics and we are looking forward to progressing this trial at some of the leading cancer centres in the U.S. as part of our ultimate goal of developing better treatments for children and adults with cancer," said Dr Taylor.

Reference List
National Institute of Health, U.S. National Library of Medicine, View Source
World Cancer Research Fund, Prostate Cancer Statistics, View Source
American Cancer Society, Cancer Statistics Center, View Source!/cancer-site/Prostate
A. Silver, I. Pellicer, W. R. Fair, W. D. Heston and C. Cordon-Cardo 1997. "Prostate-specific membrane antigen expression in normal and malignant human tissues." Clinical Cancer Research. vol. 3, 81-85, January 1997

On May 4, 2021 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biopharmaceutical company creating a new class of drugs based on targeted protein degradation, reported financial results for the first quarter ended March 31, 2021 and provided a corporate update (Press release, Arvinas, MAY 4, 2021, View Source [SID1234579035]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Last quarter we reinforced our leadership position in the targeted protein degradation space by sharing the discovery and chemical structures of ARV-110 and ARV-471 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, the first such disclosure of our clinical-stage PROTAC degraders," said John Houston, Ph.D., President and Chief Executive Officer at Arvinas. "We look forward to further demonstrating the potential of our PROTAC platform to change the lives of patients with few or no therapeutic options."

Business Highlights and Recent Developments

Presented preclinical data describing the discovery of Arvinas’ two clinical-stage PROTAC degraders, ARV-110 and ARV-471, including the first disclosures of their structures at AACR (Free AACR Whitepaper)
Anticipated Milestones and Expectations

ARV-471

Completion of the Phase 1 dose escalation (1H21)
Presentation of completed Phase 1 dose escalation data (2H21)
Interim review of safety and dose finding data from the Phase 1b trial in combination with Ibrance (palbociclib) (2H21)
Initiation of a window of opportunity study in early breast cancer (2H21)
Initiation of a combination trial of ARV-471 and another targeted therapy in 2L/3L metastatic breast cancer (2H21)
ARV-110

Completion of the Phase 1 dose escalation (1H21)
Presentation of completed Phase 1 dose escalation data (2H21)
Presentation of interim data from the ARDENT Phase 2 dose expansion at 420 mg (2H21)
Initiation of combination trial(s) with standard(s)-of-care (2021)
Other Clinical Milestones

Initiation of first-in-human study of ARV-766, an androgen receptor (AR) degrader with a differentiated profile from ARV-110, in patients with metastatic castration-resistant prostate cancer (1H21)
Financial Guidance

Based on its current operating plan, Arvinas expects its cash, cash equivalents, and marketable securities will be sufficient to fund its planned operating expenses and capital expenditures into 2024.

First Quarter Financial Results

Cash, Cash Equivalents and Marketable Securities Position: As of March 31, 2021, cash, cash equivalents and marketable securities were $651.3 million as compared with $688.5 million as of December 31, 2020. The decrease primarily related to cash used to fund operations of $43.9 million, cash used to purchase fixed assets and leasehold improvements of $1.0 million and unrealized losses of $0.8 million, partially off-set by proceeds from two collaborators of $4.0 million and proceeds from the exercise of stock options of $4.5 million.

Research and Development Expenses: Research and development expenses were $34.9 million for the quarter ended March 31, 2021 as compared with $21.7 million for the quarter ended March 31, 2020. The increase in research and development expenses for the quarter of $13.2 million primarily related to Arvinas’ continued investment in its platform, exploratory and lead optimization programs of $8.3 million, its AR program of $1.5 million and estrogen receptor program (ER) of $3.4 million.

General and Administrative Expenses: General and administrative expenses were $12.3 million for the quarter ended March 31, 2021 as compared with $7.9 million for the quarter ended March 31, 2020. The increase in general and administrative expenses for the quarter of $4.4 million related to an increase of $3.6 million in personnel and facility related costs, including $1.8 million related to stock compensation expense, and insurance, taxes and professional fees of $0.8 million.

Revenues: Revenues were $5.5 million for the quarter ended March 31, 2021 as compared with $6.2 million for the quarter ended March 31, 2020 and was generated from the license and rights to technology fees and research and development activities related to the collaboration and license agreement with Bayer that was initiated in July 2019, the collaboration and license agreement with Pfizer that was initiated in January 2018, and the amended and restated option, license and collaboration agreement with Genentech that was initiated in November 2017. The decrease in collaboration revenue of $0.7 million for the quarter was primarily related to a collaborator adding new targets that extended the period of revenue recognition for that collaboration agreement.

Net Loss: Net loss was $41.0 million for the quarter ended March 31, 2021 as compared with $21.7 million for the quarter ended March 31, 2020. The increase in net loss for the quarter ended March 31, 2021 of $19.3 million primarily related to Arvinas’ continued investment in its platform, exploratory and lead optimization programs, its AR program, its ER program, and an increase in general and administrative costs.

About ARV-110
ARV-110 is an investigational orally bioavailable PROTAC protein degrader designed to selectively target and degrade the androgen receptor (AR). ARV-110 is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer.

ARV-110 has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies.

About ARV-471
ARV-471 is an investigational orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer.

In preclinical studies, ARV-471 demonstrated near-complete ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed superior anti-tumor activity when compared to a standard of care agent, fulvestrant, both as a single agent and in combination with a CDK4/6 inhibitor.

About ARV-766
ARV-766 is an investigational orally bioavailable PROTAC protein degrader designed to selectively target and degrade AR. In preclinical studies, ARV-766 degraded all resistance-driving point mutations of AR, including L702H, a mutation associated with treatment with abiraterone and other AR-pathway therapies.

ARV-766 is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer, and ARV-766 may also have applicability in other AR-driven diseases both in and outside oncology. ARV-766 has demonstrated activity in preclinical models of resistance to currently available AR-targeted therapies.