On November 7, 2016 ChemoCentryx, Inc., (Nasdaq:CCXI), reported financial results for the third quarter ended September 30, 2016 and provided an update on the Company’s clinical development activities (Press release, ChemoCentryx, NOV 7, 2016, View Source [SID1234516363]).

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"We have made significant progress in our orphan and rare diseases portfolio — building upon our positive Phase II results in the CLEAR and CLASSIC trials in ANCA vasculitis earlier this year, we have also reported positive results in the aHUS pilot Phase II study, as well as improvement of renal function in a C3G patient who had few, if any, other treatment options. All of this provides mounting evidence that avacopan has the potential to change treatment paradigms in these rare and debilitating diseases," said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. "With avacopan in AAV, we continue to make progress regarding our regulatory discussions and remain on track to initiate our Phase III development program by the end of this year. Our scientific approach forms the foundation of a broad pipeline of promising chemoattractant-based drug candidates which we believe will transform patient care."

Pipeline Developments Across Key Therapeutic Areas

Orphan and Rare Diseases: Avacopan, an orally-administered complement inhibitor targeting the C5a receptor (C5aR), is the cornerstone of an orphan and rare diseases portfolio addressing multiple unmet medical needs. These diseases include ANCA vasculitis (AAV), atypical Hemolytic Uremic Syndrome (aHUS) and Complement 3 Glomerulopathy (C3G). Avacopan acts by blocking the destructive action of neutrophils that are activated as a consequence of the complement protein known as C5a binding to C5aR on neutrophils during autoimmune inflammatory events including the destruction of blood vessels in AAV.

Announced positive data from a pilot Phase II study designed to assess the effects of orally-administered avacopan on thrombus formation from the serum of aHUS patients with end-stage renal disease. The aHUS patients in the study are on stable chronic hemo-or peritoneal dialysis. Avacopan (30 mg) was administered twice daily for two weeks. Five patients have been treated to date. Highlights of the presentation that will take place at the American Society of Nephrology (ASN) Kidney Week 2016 include:
After 14 days of dosing the mean decrease in thrombus size was 83%. Three patients showed 100% inhibition of thrombus formation and one patient showed greater than 30% inhibition. Additionally, one patient who received only two days of avacopan treatment showed greater than 30% inhibition at that time;
Treatment appeared to be mechanism specific: when avacopan treatment was stopped, the thrombus size returned to pre-treatment levels; and
Avacopan treatment appeared to be safe; there was one serious adverse event, not considered related to avacopan use, in a patient with long-standing cardiovascular and renal disease of cardiac asystole.
Reported improvement in renal physiology and stabilization in renal function following treatment with avacopan in a patient with refractory C3G. Under a "Special Needs" protocol (similar to the compassionate use program in the United States), a C3G renal transplant recipient with deteriorating kidney function responded well to treatment with avacopan. Prior to receiving treatment with avacopan, the C3G patient had received treatment with a wide spectrum of immunosuppressant drugs including rituximab, cyclophosphamide, mycophenolate mofetil, tacrolimus and glucocorticosteroids, all of which had failed to prevent disease recurrence or progression. Highlights of the results are as follows:
After one month of avacopan treatment, renal function, based on estimated glomerular filtration rate (eGFR) stabilized, and has remained stable for over a year. Decline in a patient’s eGFR is a negative and often life-threatening effect of C3G;
Sequential kidney biopsies taken after the patient had been on avacopan for two and seven months showed continued improvement in kidney histology based on a decrease in glomerular endocapillary proliferation and a marked reduction in the number of glomerular inflammatory macrophages, as compared to the pre-treatment biopsy; and
Avacopan was shown to be safe and well tolerated. The patient has now entered month 15 of treatment and continues to tolerate avacopan well with no serious adverse events.
Conducted End-of-Phase II and scientific advice meetings with U.S. and EU regulatory agencies, respectively, regarding the avacopan AAV Phase III development plan.
Immuno-Oncology and Other Therapeutic Areas: CCX872 is a selective inhibitor of the chemokine receptor known as CCR2, and is designed to block the infiltration of immune suppressor cells in the tumor microenvironment. CCX872 is being evaluated in patients with non-resectable pancreatic cancer in an ongoing, multi-center clinical trial. The primary outcome measurement of the study is progression-free survival (PFS) after at least 24 weeks of treatment. The Company’s immuno-oncology efforts include research to identify potential drug candidates targeting additional receptors that are believed to play an important role in the tumor microenvironment. Inhibiting CCR2 may be effective in therapeutic areas beyond immuno-oncology, including decreasing inflammatory macrophage infiltration into the liver, thus reducing hepatic inflammation and fibrosis.

Presented data at the American College of Gastroenterology (ACG) 2016 Annual Meeting demonstrating that treatment with CCX872 reduced hepatic inflammation, steatosis, and scarring in models of non-alcoholic steatohepatitis (NASH). Highlights of the results are as follows:
Two models of NASH were used to determine the efficacy of CCX872 in reducing fibrosis; in both models, treatment with CCX872 achieved a statistically significant reduction in liver fibrosis as compared to placebo control;
CCX872 was more efficacious than a CCR2/CCR5 dual inhibitor, being advanced elsewhere in clinical development, in reducing liver fibrosis in a model which is known to induce NASH;
Reported initial 12 week overall response rate (ORR) results from an ongoing open label, single arm Phase Ib clinical trial with CCX872 in patients with advanced pancreatic cancer; and
Presented preclinical data at the CRI-CIMT-EATI-AACR 2016 Annual Meeting demonstrating that blocking CCR2 with CCX872 decreases tumor burden by blocking monocyte infiltration, creating a microenvironment that is more favorable for CD8+ T-cell activity. This provides a mechanistic rationale for investigating the combination of CCX872 and an immune checkpoint inhibitor for the treatment of pancreatic cancer.
Corporate Development

Announced the appointment of Henry A. McKinnell, Jr., Ph.D., retired chairman and chief executive officer of Pfizer Inc., to our Board of Directors. Dr. McKinnell brings significant leadership in operations and international strategic alliances, as well as commercial experience to ChemoCentryx.
Anticipated Milestones

Orphan and Rare Diseases:

Present detailed results from the Phase II CLEAR and CLASSIC trials of avacopan in AAV in oral presentations at ASN Kidney Week and the American College of Rheumatology (ACR) 2016 Annual Meeting, respectively;
Present results from the pilot Phase II study of avacopan in aHUS patients with end-stage renal disease at ASN Kidney Week;
Present CRISPR-Cas9 data at ASN Kidney Week, which include details of the creation of a colony of genetically unique mice that are designed to assess the effects of inhibiting the C5aR with avacopan on diseases characterized by unregulated complement activation, such as aHUS and C3G;
Finalize development plan and initiate Phase III development program of avacopan for the treatment of AAV by year end;
Initiate a clinical endpoint study with avacopan in patients with C3G in the first half of 2017; and
Initiate a clinical endpoint study with avacopan in patients with aHUS in 2017.
Immuno-Oncology and Other Therapeutic Areas:

Report PFS data from pancreatic cancer trial of CCX872 in combination with FOLFIRINOX early in the first quarter of 2017, potentially at a major medical meeting; and
Initiate a Phase II trial with CCX872 in combination with a checkpoint inhibitor in 2017.
Third Quarter 2016 Financial Results and Outlook

Cash, cash equivalents and investments totaled $131.6 million at September 30, 2016.

Revenue was $4.1 million for the three months ended September 30, 2016 compared to zero in the same period in 2015. The increase in revenue from 2015 to 2016 was due to: (i) amortization of the upfront payment from Vifor Pharma pursuant to the avacopan agreement and (ii) grant revenue from the FDA to support the clinical development of avacopan for the treatment of patients with AAV.

Research and development expenses were $8.4 million for the three months ended September 30, 2016 compared to $7.9 million reported for the same period in 2015. The increase in research and development expenses from 2015 to 2016 was primarily attributable to higher expenses associated with avacopan for start-up activities related to the Phase III development program in patients with AAV. This increase was partially offset by lower expenses associated with Phase II development of avacopan, due to the completion of the CLEAR and CLASSIC Phase II clinical trials in 2016.

General and administrative expenses were $3.2 million for the three months ended September 30, 2016 compared to $3.8 million for the comparable period in 2015. The decrease from 2015 to 2016 was primarily due to lower stock-based compensation and intellectual property filing expenses.

Net loss was $7.1 million for the second quarter ended September 30, 2016 compared to $11.7 million in the same period in 2015.

Total shares outstanding at September 30, 2016 were approximately 47.8 million shares.