On November 4, 2019 Ascentage Pharma (6855.HK), a globally-focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, hepatitis B virus and age-related diseases, reported a combination therapy strategic collaboration with Henlius (2696.HK), working together to conduct clinical trials of the combination therapy between APG-2575, a novel, orally administered Bcl-2 selective inhibitor developed by Ascentage Pharma, and HLX01 (Rituximab Injection), the first launched product by Henlius, for the treatment of chronic lymphocytic leukemia (CLL) in the People’s Republic of China (Press release, Ascentage Pharma, NOV 4, 2019, View Source [SID1234550229]).

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!

APG-2575 is a novel, orally administered Bcl-2 selective inhibitor developed by Ascentage Pharma. It is designed to treat hematologic malignancies by selectively blocking Bcl-2 to restore the normal apoptosis process in cancer cells. In July 2019, the first patient was dosed successfully in a Phase I clinical trial of APG-2575 for the treatment of hematologic malignancies in China, making APG-2575 potentially the first China-made Bcl-2 inhibitor to enter clinical study. CLL and non-Hodgkin’s lymphoma (NHL) patients are included in this trial. The Phase I clinical trial of APG-2575 in hematologic malignancies has already been initiated in Australia and the U.S. As of Aug. 13, 2019, one patient’s tumor had been reduced in size by over 60%, a response that met the criteria for partial response (PR); there were three patients in the 400mg dose cohort whose absolute lymphocyte counts (ALC), another key efficacy parameter of this study, have reached the criteria for complete response (CR) by the end of cycle 1. No tumor lysis syndrome (TLS) was observed in the study, indicating the favorable safety profile of the investigational agent. Moreover, at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, Ascentage Pharma has already presented results from several preclinical studies that demonstrated APG-2575’s potential in combination therapies.

As the first approved biosimilar in China, HLX01 (Rituximab Injection) is mainly for the treatment of non-Hodgkin’s lymphoma (NHL). In February 2019, China National Medical Products Administration (NMPA) approved HLX01 (Rituximab Injection) for the treatment of adult patients with 1) relapsed or refractory, follicular lymphoma; 2) previously untreated stages III-IV follicular, non-Hodgkin’s lymphoma; and 3) CD20-positive, diffuse large B-cell, non-Hodgkin’s lymphoma (DLBCL), namely all the approved indications of the originator Rituximab in China. Rituximab in combination with chemotherapy has long been the standard treatment of NHL. HLX01 (Rituximab Injection) provides an alternative treatment option for lymphoma patients, as over 1,000 patients benefited in the first month after its commercial launch.

The collaboration is of great significance to both companies. Bcl2 inhibitors are a rising star for B cell malignancies and can be applied to the treatment of CLL in combination with rituximab. Potentially this combination could also be extended to other B cell malignancies

Dr. Dajun Yang, Chairman and CEO of Ascentage Pharma, commented: "We are delighted to be entering this collaboration agreement with Henlius. As the first China-made Bcl-2 inhibitor to enter clinical study, APG-2575 is a key candidate in our development pipeline of apoptosis with a great potential in the treatment of hematologic malignancies. HLX01 (Rituximab Injection), as the first approved biosimilar in China, provides a new treatment option for lymphoma patients. Combination therapy is going to be the trend in future. The teams from Ascentage Pharma and Henlius will work closely to explore the clinical utility of this combination therapy. We hope APG-2575 combined with HLX01 will demonstrate synergistic effect in the treatment of CLL, and thereby offer additional treatment options for Chinese patients."

"We are excited to reach the agreement with Ascentage Pharma," said Scott Liu, Ph.D., Co-founder, President and CEO of Henlius. "As the first approved and marketed product of Henlius, HLX01 (Rituximab Injection) is approved for all the indications of the originator rituximab in China, thus providing alternative options for lymphoma patients. APG-2575 is indicated for multiple hematologic malignancies as mono-therapy and shows great potential in combination therapy. We expect the two products to join hand in hand in the treatment of CLL. In future, Henlius and Ascentage Pharma will press forward with the combination therapy, and provide more treatment options for patients in China."

On November 4, 2019 Harbour BioMed (HBM) reported the start of the first clinical trial of its next-generation fully human anti-CTLA-4 antibody (HBM4003) for the treatment of patients with advanced solid tumors (Press release, Harbour BioMed, NOV 4, 2019, View Source [SID1234550228]). This trial is the first with a fully human antibody based on heavy chain only antibody technology (HCAb). HBM4003 has shown potential for increased anti-tumor activity based on enhanced antibody dependent cell toxicity (ADCC) mediated Treg depletion and a favorable safety profile resulting from reduced half-life.

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 preclinical studies, HBM4003 demonstrated potent anti-tumor activity with much lower systemic drug exposure, suggesting a potentially significant improvement in its therapeutic profile. HBM presented preclinical study results of HBM4003 in April 2019 at the annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). The trial is design led to assess the safety, pharmacokinetic profile and preliminary anti-tumor activity of HBM4003 in patients with advanced solid tumors.

"HBM4003, based on our proprietary human HCAb platform, underscores the potential for heavy chain only antibodies in developing the next-generation of immuno-oncology therapeutics for patients," said Dr. Jingsong Wang, Founder, Chairman and CEO of Harbour BioMed. "This study, being conducted in Australia, is the first part of a global development program, with US and China clinical trials — including combination studies — expected to begin in the near future." Dr. Wang added, "HBM is rapidly building its pipeline, with HBM4003 advancing to the clinic in less than three years and with additional mono- and bi-specific antibodies against various targets in pre-clinical development."

CTLA-4 is one of the major negative regulators of T-cell responses. Anti-CTLA-4 antibodies are immune checkpoint inhibitors with proven value in cancer immunotherapy by increasing T-cell activity to attack tumor cells. Despite demonstrated efficacy, their safety profiles have been a barrier to broader application as both mono- and combination therapies. Preclinical studies have shown that HBM4003’s immune stimulatory activity is driven by two mechanisms: depletion of immune suppressing Treg through enhanced ADCC and; inhibition of negative signaling from the interaction of CTLA-4 with the co-stimulatory molecule B7.

"Advanced solid tumors including melanoma remain a major challenge despite improvements in the standard of care," said Prof. Paul de Souza, Dean of Medicine at the University of Wollongong Australia, and a principal investigator for this study. "Preclinical studies of HBM4003 have shown great potential. This trial provides the first opportunity to evaluate how this promising compound will perform in the treatment of solid tumors."

About Heavy Chain Only Antibodies (HCAb)

Heavy-chain only antibodies consist only of two heavy chains; they lack the two light chains usually found in traditional antibodies. HCAb’s are smaller than conventional antibodies, potentially allowing for increased tissue penetration. These antibodies also maintain IgG-like pharmacokinetic properties and immune activation (Fc) functions. HCAbs can bind antigens despite having only VH domains and have shown similar specificity to regular antibodies.

HBM’s HCAbs, which are generated by its fully human transgenic mouse platform, further enable the design of versatile formats of antibodies capable of addressing different mechanisms of action and use in different applications. HCAbs are naturally generated human antibodies against desired targets; thus there is no need for humanization to reduce immunogenicity.

On November 4, 2019 ChemoCentryx, Inc., (Nasdaq:CCXI), reported financial results for the third quarter ended September 30, 2019 and provided an overview of the Company’s recent corporate highlights (Press release, ChemoCentryx, NOV 4, 2019, View Source [SID1234550227]).

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!

"Strong and swift is the pace of our progress as we eagerly anticipate topline data from our Phase III pivotal ADVOCATE trial of avacopan in ANCA vasculitis," said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. "At our recent R&D Day in New York the stage was set for the upcoming data, as our schedule featured two pre-eminent nephrologists as well as an ANCA vasculitis patient who highlighted the patient journey, the disease burden and the noxious consequences of chronic steroid use as part of the current standard-of-care. We provided a comprehensive overview of ANCA disease assessment and therapeutic improvement—ranging from the primary endpoints, BVAS remission at 26 and 52 weeks, to key secondary endpoints in the trial, as we aim to demonstrate a new way to treat this deadly disease."

"Furthermore, topline data from ADVOCATE is just the first in a cadence of five data readouts expected between now and the end of 2020. These readouts include those from the LUMINA-1 and LUMINA-2 trials of our CCR2 inhibitor, CCX140, in Focal Segmental Glomerulosclerosis (FSGS), the ACCOLADE trial of avacopan in C3 Glomerulopathy (C3G) and the AURORA trial of avacopan in Hidradenitis Suppurativa (HS). Our financial position is strong, enabling this historic period of data readouts. We look forward to a time soon where our innovations can be brought to the real service of our patients, to the aid of clinicians and to the benefit of those who have invested in this inventive enterprise."

Recent Highlights

Remained on track for mid-to-late Q4 topline data from the ADVOCATE global Phase III trial of avacopan in 331 patients with ANCA-associated vasculitis.

Completed enrollment in the Company’s LUMINA-1 Phase II randomized clinical trial of CCX140, an inhibitor of the chemokine receptor known as CCR2, in patients with sub-nephrotic primary Focal Segmental Glomerulosclerosis (FSGS), another rare kidney disease. Topline data is

anticipated in the first half of 2020. The single-arm, open label LUMINA-2 study continues to enroll, evaluating CCX140 in primary FSGS patients with the more severe nephrotic levels of proteinuria.

Awarded a two-year $1 million grant from the orphan drug office of the FDA to support advancement in the Company’s ACCOLADE Phase II clinical trial of avacopan in patients with the rare kidney disease C3 Glomerulopathy, a disease with no effective approved treatment. Approaching 60 percent enrollment in the ACCOLADE trial.

Attended Symposium on Hidradenitis Suppurativa Advances (SHSA), held November 1-3 in Detroit, Michigan. The Company’s AURORA Phase IIb clinical trial of avacopan for the treatment of the chronic disabling skin disease Hidradenitis Suppurativa (HS) is progressing well, with almost 80 percent of sites now activated and over 55 percent of patients enrolled to date.

Third Quarter 2019 Financial Results

Revenue was $10.6 million for the third quarter of 2019, compared to $9.0 million for the same period in 2018. Revenue is recognized based on the proportionate amount of costs incurred as a percentage of total budgeted costs to fulfill the performance obligations under the Company’s avacopan and CCX140 commercialization agreements with Vifor Pharma.

Research and development expenses were $18.1 million for the third quarter of 2019, compared to $15.1 million for the same period in 2018. The increase from 2018 to 2019 was primarily attributable to patient enrollment of the avacopan AURORA Phase II clinical trial in patients with HS and the two CCX140 LUMINA Phase II clinical trials in patients with FSGS, partially offset by decreases in research and drug discovery expenses.

General and administrative expenses were $6.1 million for the third quarter of 2019, compared to $5.4 million for the same period in 2018. The increase from 2018 to 2019 was primarily due to higher employee-related expenses, including those associated with our commercialization planning efforts, and higher professional fees.

Net loss for the third quarter of 2019 was $12.9 million, compared to $10.9 million for the same period in 2018.

Total shares outstanding at September 30, 2019 were approximately 58.3 million shares.

Cash, cash equivalents and investments totaled $205.8 million at September 30, 2019. The Company expects to close 2019 with cash and investments in excess of $185 million.

Conference Call and Webcast

The Company will host a conference call and webcast today, November 4, 2019 at 5:00 p.m. Eastern Time / 2:00 p.m. Pacific Time. To participate by telephone, please dial (877) 303-8028 (Domestic) or (760) 536-5167 (International). The conference ID number is 5867903. A live and archived audio webcast can be accessed through the Investors section of the Company’s website at www.ChemoCentryx.com. The archived webcast will remain available on the Company’s website for fourteen (14) days following the conference call.

On November 4, 2019 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 third quarter of 2019 and provided a corporate update (Press release, Arvinas, NOV 4, 2019, View Source [SID1234550226]).

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!

"We recently became the first company to present clinical data on a targeted protein degrader, sharing initial data on our first two oncology programs. In addition, we shared preclinical data demonstrating that brain-penetrant PROTAC protein degraders could degrade pathologic tau in vivo, further demonstrating the potential of our PROTAC platform," said John Houston, Ph.D., Chief Executive Officer of Arvinas. "We look forward to the continued progress of our lead programs and pipeline, and ultimately to making a difference in the lives of patients."

Business Highlights and Recent Developments

Presented initial data from the company’s ongoing Phase 1 clinical trials of ARV-110 and ARV-471. The initial data showed dose proportionality for ARV-110 and that exposures of both ARV-110 and ARV-471 have reached levels associated with tumor growth inhibition in preclinical studies. In addition, both ARV-110 and ARV-471, at each dose tested to date, were well tolerated, with no dose-limiting toxicities and no observed grade 2, 3, or 4 adverse events related to treatment.
Presented preclinical data from the company’s alpha-synuclein (a-synuclein)-targeted PROTAC protein degrader program. The data showed that the company has created a-synuclein-targeted degraders that degrade oligomeric a-synuclein. In addition, the company has created a-synuclein-targeting PROTAC protein degraders that cross the blood-brain barrier following parenteral (peripheral) administration.
Announced that six new oncology and neurology thought leaders in the areas of oncology and neurological disorders have joined the company’s scientific advisory board (SAB). The new members are Tomasz M. Beer, M.D., F.A.C.P., Adam L. Boxer, M.D., Ph.D., Sara Courtneidge, Ph.D., Lennart Mucke, M.D., Benjamin G. Neel, M.D., Ph.D., and Lillian L. Siu, M.D. For full details on our new SAB members, visit www.arvinas.com.
Initiated patient dosing in its ongoing Phase 1 clinical trial of ARV-471, which is evaluating the safety, tolerability, and pharmacokinetics of ARV-471 in patients with locally advanced or metastatic ER positive / HER2 negative breast cancer.
Anticipated Milestones and Expectations

For the ARV-110 program, Arvinas expects to next share completed Phase 1 dose escalation clinical data in the first half of 2020.
For the ARV-471 program, Arvinas expects to next share clinical data in the second half of 2020.
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 expenditure requirements into the second half of 2021.

Financial Highlights

Cash, Cash Equivalents, and Marketable Securities Position: As of September 30, 2019, cash, cash equivalents, and marketable securities were $190.5 million as compared to $187.8 million as of December 31, 2018. The increase in cash, cash equivalents and marketable securities of $2.7 million in the first nine months of 2019 primarily related to aggregate proceeds of $51.5 million from a collaboration and license agreement with Bayer and the issuance of common stock to Bayer, partially offset by the purchase of lab equipment and leasehold improvements of $4.5 million and cash used to fund operations of $49.7 million.

Research and Development Expenses: Research and development expenses were $16.6 million for the quarter ended September 30, 2019, as compared to $13.1 million for the quarter ended September 30, 2018. The increase in research and development expenses for the quarter primarily related to expenses associated with our ongoing Phase 1 clinical trial of ARV-110 and the initiation of our Phase 1 clinical trial of ARV-471 as well as increased personnel and other expenses related to our platform research and exploratory programs research.

General and Administrative Expenses: General and administrative expenses were $8.0 million for the quarter ended September 30, 2019, as compared to $4.3 million for the quarter ended September 30, 2018. The increase in general and administrative expenses for the quarter was primarily related to increased employee expenses and other compliance costs associated with becoming a public company in the fourth quarter of 2018.

Revenues: Revenue was $30.1 million for the quarter ended September 30, 2019, as compared to $3.4 million for the quarter ended September 30, 2018. Revenue for the quarter ended September 30, 2019 included $24.7 million of revenue recognized from the Arvinas contribution of the license to the joint venture between Bayer and Arvinas to pursue the PROTAC technology in agricultural applications (the "Joint Venture"). The remaining revenue of $5.4 million for the quarter 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.

Loss from Equity Method Investment: Loss from equity method investment for the quarter ended September 30, 2019 was $24.7 million, which related to the loss from the equity method investment in the Joint Venture. The loss was generated from the Joint Venture’s expensing the values associated with the contributed intellectual property from the Joint Venture partners.

Net Loss: Net loss was $17.7 million for the quarter ended September 30, 2019, as compared to $13.4 million for the quarter ended September 30, 2018. The increased revenue that related to the Joint Venture was offset by the loss from equity method investment in the Joint Venture for the quarter ended September 30, 2019 and as such, the increase in net loss for the quarter was primarily due to increased research and development expenses and increased general and administrative expenses.

About ARV-110
ARV-110 is an 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 (mCRPC). Arvinas’ Phase 1 trial of ARV-110 will assess its safety, tolerability, and pharmacokinetics, and will also include measures of anti-tumor activity and pharmacodynamic readouts as secondary endpoints.

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 a PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of women with metastatic breast cancer. Arvinas’ Phase 1 trial of ARV-471 will assess its safety, tolerability, and pharmacokinetics, and will also include measures of anti-tumor activity and pharmacodynamic readouts as secondary endpoints.

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 as a single agent and in combination with a CDK4/6 inhibitor when compared to a standard of care agent, fulvestrant (as a single agent and in combination with a CDK4/6 inhibitor).

On November 4, 2019 Agilent Technologies Inc. (NYSE: A) reported that it will release fourth quarter fiscal year 2019 financial results after the stock market closes on November 25 (Press release, Agilent, NOV 4, 2019, https://www.agilent.com/about/newsroom/presrel/2019/04nov-gp19023.html [SID1234550225]). The company will also host a live webcast of its investor conference call in listen-only mode.

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!

Date: Monday, November 25, 2019
Time: 1:30 PM (Pacific Time)
Web access: www.investor.agilent.com

To listen to the call online, select the "Q4 2019 Agilent Technologies Inc. Earnings Conference Call" link in the "News & Events — Events" portion of the Investor Relations section of the Agilent website. The webcast will remain on the company site for 90 days.

In addition, Agilent will be hosting the following upcoming webcasts for the investment community.

Piper Jaffray 31st Annual Healthcare Conference
Wednesday, December 4, at 8:30 a.m. (ET)
Lotte New York Palace, New York
Bob McMahon, Agilent chief financial officer

Evercore ISI 2nd Annual HealthCONx
Thursday, December 5, at 8:00 a.m. (ET)
Four Seasons Boston, Boston, Mass.
Bob McMahon, Agilent chief financial officer

Links to join the webcasts will be available in the "News & Events — Events" portion of the Investor Relations section of the Agilent website.