On May 12, 2021 Checkpoint Therapeutics, Inc. ("Checkpoint") (NASDAQ: CKPT), a clinical-stage immunotherapy and targeted oncology company, reported the completion of enrollment for the metastatic cutaneous squamous cell carcinoma ("cSCC") cohort in its registration-enabling clinical trial of anti-PD-L1 antibody, cosibelimab (Press release, Checkpoint Therapeutics, MAY 12, 2021, View Source [SID1234579815]).

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!

In January 2020, Checkpoint announced that the U.S. Food and Drug Administration had confirmed the registration submission pathway for cosibelimab in metastatic cSCC based on the ongoing clinical trial, which has a target enrollment of approximately 75 patients and a primary efficacy endpoint of confirmed objective response rate assessed by independent central review. Top-line results are expected in the fourth quarter of 2021 and, upon a successful outcome, Checkpoint intends to submit a Biologics License Application ("BLA") for cosibelimab in the first half of 2022, followed shortly thereafter by a Marketing Authorization Application submission in Europe. Additionally, Checkpoint continues to enroll a registration-enabling cohort of patients with locally advanced cSCC and anticipates that this second indication will also be included in the planned BLA and MAA submissions next year.

James F. Oliviero, President and Chief Executive Officer of Checkpoint, stated, "We are pleased to report the completion of enrollment for our metastatic cSCC cohort, with over 75 patients enrolled, which we expect will enable a readout of top-line results in the fourth quarter of this year." Mr. Oliviero continued, "Based on the interim data presented last year at the European Society for Medical Oncology ("ESMO") Virtual Congress 2020 and the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) ("SITC") 35th Anniversary Annual Meeting, we believe cosibelimab has the potential to be a best-in-class anti-PD-L1 antibody, which we intend to commercialize at a substantially lower price in comparison to currently marketed anti-PD-(L)1 therapies. With a compelling safety and efficacy profile, as well as our market disruptive pricing strategy, we believe cosibelimab can achieve meaningful and rapid market share in the $25 billion and growing PD-(L)1 class."

About Cutaneous Squamous Cell Carcinoma
cSCC is the second most common human cancer in the United States, with an estimated annual incidence of 700,000 cases. While most cases are localized tumors amenable to curative resection, approximately 8% of patients will experience a local recurrence, 5% of patients will develop nodal metastases, and an estimated 2% of patients will die from their disease. Ten-year survival rates are less than 20% for patients with regional lymph-node involvement. For those patients who develop distant metastases, the median survival time is estimated to be less than two years. In addition to being a life-threatening disease, cSCC causes significant functional morbidities and cosmetic deformities based on tumors commonly arising in the head and neck region and invading blood vessels, nerves and vital organs such as the eye or ear.

About Cosibelimab
Cosibelimab (formerly referred to as CK-301) is a potential best-in-class, high affinity, fully-human monoclonal antibody of IgG1 subtype that directly binds to programmed death ligand-1 ("PD-L1") and blocks the PD-L1 interaction with the programmed death receptor-1 ("PD-1") and B7.1 receptors. Cosibelimab’s primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptors PD-1 and B7.1, which removes the suppressive effects of PD-L1 on anti-tumor CD8+ T-cells to restore the cytotoxic T cell response. Cosibelimab is potentially differentiated from the currently marketed PD-1 and PD-L1 antibodies through sustained >99% target tumor occupancy to reactivate an antitumor immune response and the additional benefit of a functional Fc domain capable of inducing antibody-dependent cell-mediated cytotoxicity ("ADCC") for potential enhanced efficacy in certain tumor types.

On May 12, 2021 Sosei Group Corporation ("the Company") (TSE: 4565) provides an update on operational activities and reported its consolidated results for the first quarter ended 31 March 2021 (Press release, Sosei, MAY 12, 2021, View Source [SID1234579832]). The full report can be accessed by clicking here.

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!

Shinichi Tamura, Chairman, President and CEO of Sosei Heptares, commented: "We continue to make good progress expanding our drug discovery business and remain well positioned to capitalize on a range of growth opportunities. We have initiated several exciting new technology collaborations designed to enhance our world-leading discovery platform and extend the reach of its application, including beyond GPCRs for the first time. We have made good progress with our partnered programs, which have delivered multiple milestones and generated important revenues since the start of the year. Meanwhile, our inhouse programs provide us with a rich source of future partnering opportunities that we are exploring. We have ambitious plans and expect 2021 to be a year of increased investment in strategic growth initiatives, both organic and inorganic, and believe we have the right strategy to deliver continued success and value creation for all stakeholders."

Operational Highlights for Q1 2021

New strategic technology collaboration with PharmEnable for AI-driven drug discovery – aim to identify new leads against a challenging "peptidergic" GPCR target
First strategic collaboration to explore SBDD approaches beyond GPCRs with Metrion Biosciences – collaboration targeting ion channels, a large, under-exploited target class where structural input to drug discovery has been limited. Drug discovery program to identify novel, highly specific leads for further development against a single ion channel associated with neurological diseases.
Worldwide rights to out-licensed muscarinic agonist programs regained from AbbVie/Allergan – independent review of programs has completed, with increased investment allocated to advance the HTL0016878 selective muscarinic M4 agonist through clinical studies and build value ahead of future partnering. HTL0016878 represents a unique opportunity to develop a novel therapeutic with a new mechanism of action for neurological disorders including schizophrenia. Negotiations for collaborations on this and other muscarinic programs are now in progress.
Two milestone payments totalling US$4 million received from Genentech during Q1 2021 – milestones achieved from the delivery of StaR proteins based on nominated targets under the 2019 multi-target agreement.
Spin-off company Orexia Therapeutics merged into Centessa Pharmaceuticals, a new asset-centric company – Orexia became one of ten private companies merged into Centessa, which launched in February 2021 and raised US$250 million. Sosei Heptares’ equity holding in Orexia was converted into a proportional shareholding in Centessa, which filed for an Initial Public Offering on Nasdaq in April 2021.
US$2.5 million milestone received from Formosa Pharmaceuticals – based on progression of APP13007, a divested asset, into Phase 3 trials as a new potential treatment for pain and inflammation following cataract surgery.
Financial Highlights for the Three-month Period ended 31 March 2021

Revenue totalled JPY 1,207 million (US$11.4 million*), an increase of JPY 45 million (US$0.7 million) vs. the prior corresponding period. The increase was due to (i) the achievement of two milestones totalling US$4.0 million in Q1 2021 relating to the delivery of StaR proteins provided to Genentech (in respect of which US$2.1 million has been recognised) vs. the achievement of one US$1.5 million milestone in Q1 2020, and (ii) larger releases of deferred revenue in Q1 2021 due to there being an additional contract in the current quarter in respect of which revenue had been deferred in the past (AbbVie).
Cash R&D expenses totalled JPY 1,102 million (US$10.4 million), an increase of JPY 545 million (US$5.3 million) vs. the prior corresponding period. The increase relates primarily to (i) spend on new innovative research collaborations, including Metrion, PharmEnable and Captor; (ii) an expansion in R&D headcount to support the growth of the business; (iii) a low level of spend in the comparative period, which included some non-recurring credits, including the successful resolution of disputed costs charged by one supplier; and (iv) a stronger GBP vs. JPY.
Cash G&A expenses totalled JPY 641 million (US$6.0 million), an increase of JPY 204 million (US$2.0 million) vs. the prior corresponding period. The increase is primarily due to an increase in personnel related expenses. In the prior corresponding period, personnel related expenses were lower as a result of a reduction in the UK share based payment related National Insurance liability, which was driven by share price movements in that particular quarter.
Cash earnings net loss** totalled JPY 683 million (US$6.4 million), vs. a cash profit of JPY 12 million (US$0.1 million) in the prior corresponding period. The main reason for the increase in the operating loss is that the increase in Cash R&D and G&A costs exceeded the increase in revenue.
Operating loss totalled JPY 1,238 million (US$11.7 million) (vs. an operating loss of JPY 445 million (US$4.1 million in the prior corresponding period). The main reason for the increase in the operating loss is that the increase in operating expenses exceeded the increase in revenue.
Net loss totalled JPY 1,153 million (US$10.9 million) vs. a net loss of JPY 746 million (US$6.9 million) in the prior corresponding period. The main reason for the net loss is the increase in operating loss (for the reasons stated above).
Cash and cash equivalents as at March 31, 2021 increased by JPY 388 million (US$3.7 million) from the beginning of the year and amounted to JPY 40,396 million (US$364.8 million).
*Convenience conversion to US$ at the following rates: 2021: 1US$ =106.092 JPY; 2020: 1US$ =108.907 JPY

On May 12, 2021 Caelum Biosciences and Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) reported that two abstracts on CAEL-101, a potentially first-in-class amyloid fibril targeted therapy, have been accepted for e-poster presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress 2021, taking place virtually from June 9 to 17, 2021 (Press release, Alexion, MAY 12, 2021, View Source [SID1234579765]). Both presentations will include new data from the Phase 2 open-label dose escalation study evaluating the safety and tolerability of CAEL-101 in combination with standard-of-care (SoC) therapy in AL amyloidosis. One will feature data studying safety and tolerability in AL amyloidosis patients treated with 1000 mg/m2 CAEL-101 in combination with cyclophosphamide-bortezomib-dexamethasone plus daratumumab. The second will include new data further supporting the selection of the 1000 mg/m2 dose for the ongoing Phase 3 study and demonstrating the possible stabilization of cardiac disease as assessed by Mayo staging.

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 abstracts accepted for e-poster presentations are listed below and are now available on the EHA (Free EHA Whitepaper) website. All e-poster presentations will be made available on the virtual congress platform on June 11, 2021 at 09:00 a.m. CEST (3:00 a.m. EDT) and will be available throughout the duration of the Congress.

Safety and Tolerability of CAEL-101 in Combination with Cyclophosphamide-Bortezomib-Dexamethasone and Daratumumab in Patients with AL Amyloidosis. Abstract #EP1017– e-poster presentation; session title: Myeloma and other monoclonal gammopathies – Clinical.

Safety and Tolerability of CAEL-101 in Patients with AL Amyloidosis in a Phase 2 Study for a Median of 38 Weeks. Abstract #EP1018 – e-poster presentation; session title: Myeloma and other monoclonal gammopathies – Clinical.

As was previously announced, the Cardiac Amyloid Reaching for Extended Survival (CARES) Phase 3 clinical program to evaluate CAEL-101 in combination with SoC therapy in AL amyloidosis has begun. Enrollment is underway in two parallel Phase 3 studies – one in patients with Mayo stage IIIa disease (ClinicalTrials.gov Identifier: NCT04512235) and one in patients with Mayo stage IIIb disease (ClinicalTrials.gov Identifier: NCT04504825) – and will collectively enroll approximately 370 patients globally. The Phase 2 program continues with the ongoing evaluation of CAEL-101 in combination with SoC therapy plus daratumumab.

About CAEL-101

CAEL-101 is a first-in-class monoclonal antibody (mAb) designed to improve organ function by reducing or eliminating amyloid deposits in the tissues and organs of patients with AL amyloidosis. The antibody is designed to bind to misfolded light chain protein and amyloid and shows binding to both kappa and lambda subtypes. In a Phase 1a/1b study, CAEL-101 demonstrated improved organ function, including cardiac and renal function, in 27 patients with relapsed and refractory AL amyloidosis who had previously not had an organ response to standard of care therapy. CAEL-101 has received Orphan Drug Designation from both the U.S. Food and Drug Administration and European Medicine Agency as a potential therapy for patients with AL amyloidosis.

About AL Amyloidosis

AL amyloidosis is a rare systemic disorder caused by an abnormality of plasma cells in the bone marrow. Misfolded immunoglobulin light chains produced by plasma cells aggregate and form fibrils that deposit in tissues and organs. This deposition can cause widespread and progressive organ damage and high mortality rates, with death most frequently occurring as a result of cardiac failure. Current standard of care includes plasma cell directed chemotherapy and autologous stem cell transplant, but these therapies do not address the organ dysfunction caused by amyloid deposition, and up to 80 percent of patients are ineligible for transplant.

AL amyloidosis is a rare disease but is the most common form of systemic amyloidosis. There are approximately 22,000 patients across the United States, France, Germany, Italy, Spain and the United Kingdom. AL amyloidosis has a one-year mortality rate of 47 percent, 76 percent of which is caused by cardiac amyloidosis.

On May 12, 2021 PerkinElmer, Inc. (NYSE: PKI) reported it has entered into an agreement to acquire Nexcelom Bioscience for $260 Million in cash (Press release, PerkinElmer, MAY 12, 2021, View Source [SID1234579798]). The transaction is expected to close during the second quarter of 2021.

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!

Nexcelom is a leading, global provider of automated cell counting instruments, image cytometry workstations, assays and a variety of cell reagents, consumables, and fit-for-purpose cell counting method selection and development instructions that follow ISO Cell Counting Standards and aid in the development of cell and gene and immuno-oncology therapies, virology drugs and vaccines.

Headquartered in Lawrence, Massachusetts, Nexcelom is founder-led, privately held and has approximately 130 employees around the world based in the U.S., the UK and China. Nexcelom’s expected 2021 revenues are approximately $40 Million.

Commenting on the transaction, Prahlad Singh, president and chief executive officer of PerkinElmer said, "We are looking forward to bringing Nexcelom’s expertise and technologies in drug development together with our passion and solutions for drug discovery. This combination will expand our efforts to help academic, government and biopharmaceutical organizations streamline their complete workflows and support efforts to accelerate time to target and time to market for novel therapies."

Dr. Peter Li, president and chief executive officer of Nexcelom added, "Our team is very excited to be joining forces with PerkinElmer to help scientists resolve some of today’s most pressing health challenges through modernizing cell based assays using the most advanced cell models. Our organization has a deep commitment to innovation and we are looking forward to continuing to grow our technology and customer footprint in combination with PerkinElmer’s strong global presence and infrastructure."

PerkinElmer’s existing biologics, vaccine and cell and gene research solutions feature industry-leading high content, in vivo, and cell painting screening technologies; innovative immunoassays; CRISPR, RNAi and DNA tools and custom cell lines; cell plate readers and advanced automation; microfluidics and analytical platforms.

The agreement to acquire Nexcelom comes just five months after PerkinElmer added Horizon Discovery, a leader in gene editing and modulation. To learn more about PerkinElmer’s full range of life sciences solutions, informatics and OneSource services please visit: View Source

On May 12, 2021 Leap Therapeutics (Nasdaq: LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, and Flagship Biosciences, the leader in data-centric pathology and tissue analysis, reported that they have developed an image analysis RNAscope assay that is being used successfully for prospective patient enrollment in a clinical trial (Press release, Leap Therapeutics, MAY 12, 2021, View Source [SID1234579816]). To the companies’ knowledge, this is the first example of an RNAscope assay using a digital image analysis solution for patient enrollment. The findings were published in an article, "Validation of a DKK1 RNAscope chromogenic in situ hybridization assay for gastric and gastroesophageal junction adenocarcinoma tumors," on Monday, May 10 in Scientific Reports. It can be viewed at View Source

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!

Co-authored by a collaborative team from Leap Therapeutics, Flagship Biosciences, and Athenaeum Pathology Consulting, the article highlights how Leap is identifying patients likely to benefit from DKN-01, its anti-Dickkopf-1 (DKK1) antibody, and Flagship’s ability to validate and implement complex biomarker assays using digital image analysis. Leap and Flagship’s work centered on the development and validation of a DKK1 RNAscope chromogenic in situ hybridization (CISH) assay and digital image analysis solution. DKK1 is a secreted modulator of Wnt signaling that is frequently overexpressed in tumors and associated with a poor prognosis for patients. DKN-01 is a humanized monoclonal therapeutic antibody that binds to and blocks the activity of DKK1 and has demonstrated clinical activity in gastric/gastroesophageal junction (G/GEJ) adenocarcinoma patients with elevated tumoral expression of DKK1 RNA. Leap and Flagship have validated the DKK1 RNAscope assay and accompanying digital image analysis solution as specific, sensitive, accurate, and reproducible according to Clinical Laboratory Improvement Amendments (CLIA) guidelines, and their work is currently being applied to prospectively identify G/GEJ patients with elevated tumoral expression of DKK1 for treatment with a DKN-01 plus tislelizumab combination (Leap Therapeutics; NCT04363801). Additionally, the companies are using the DKK1 RNAscope assay and digital image analysis solution for a retrospective analysis of G/GEJ patients treated with DKN-01 in combination with tislelizumab and chemotherapy.

Biomarkers are increasingly prominent in drug development and are often applied in clinical trial design to determine the patients who are most likely to benefit from a specific therapeutic or treatment regimen. To use a biomarker strategy to prospectively identify patients, the biomarker test must be robust and precise. Because of the challenges in manual semi-quantification of RNAscope tissue staining, Leap and Flagship developed the novel digital image analysis algorithm that identifies tumor cells and quantifies DKK1 signal.

"A potential challenge with RNAscope is manual scoring, which requires a pathologist to score the tissue at a high magnification to visualize and count the number of stained dots that appear in tumor cells," said Michael Kagey, Ph.D., Senior Director of Translational Medicine at Leap Therapeutics. "Since this can lead to slow, inaccurate, and non-reproducible scoring, we worked with Flagship to develop a digital algorithm. The digital algorithm reduces pathologist time, potential variability from manual scoring and allows us to reliably screen for patients who may benefit from our therapy."

In addition to the prospective screening of patients, the work is also further advancing the companion diagnostic development of the RNAscope assay and could generally be used as a guide for the validation of RNAscope CISH assays with digital image quantification.

"Our technology, combined with our scientific process and pathology oversight allows you to quickly find the right patients and get to your endpoints more rapidly," said Trevor Johnson, CEO of Flagship Biosciences. "Image analysis also provides a superior return on investment by saving time and helping get drugs to market more quickly. Our ability to take a completely novel pathology approach and turn it into a CLIA-validated diagnostic test to help our clients is extremely gratifying."

"Our clinical development has been enhanced by the rapid, prospective patient screening that has happened as a result of using the DKK1 RNAscope CISH assay and digital image analysis solution," said Douglas E. Onsi, President and CEO of Leap Therapeutics. "As a result of the partnership between Leap and Flagship, the patients who we believe will best benefit from our drug are now being included in our trial. We look forward to further collaborating with Flagship Biosciences."