On August 7, 2018 Array BioPharma Inc. (NASDAQ: ARRY) reported it has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for encorafenib (BRAFTOVI), in combination with binimetinib (MEKTOVI) and cetuximab for the treatment of patients with BRAFV600E-mutant metastatic colorectal cancer (mCRC) as detected by an FDA-approved test, after failure of one to two prior lines of therapy for metastatic disease (Press release, Array BioPharma, AUG 7, 2018, View Source [SID1234528516]). BRAFV600E-mutant mCRC patients have a mortality risk more than double that of mCRC patients without the mutation, and currently there are no therapies specifically approved for this high unmet need population. [1-6]

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Breakthrough Therapy Designation is an FDA process designed to expedite the development and review of drugs that are intended to treat a serious condition where preliminary clinical evidence indicates that they may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

"We are delighted that the FDA has recognized the potential of this combination for patients with BRAFV600E-mutant metastatic colorectal cancer," said Victor Sandor, M.D., Chief Medical Officer. "As there are no regimens approved specifically for BRAFV600E-mutant mCRC, this designation provides us with the opportunity to work closely with the FDA to potentially accelerate our effort to bring an important treatment option to these patients in critical need."

As presented at the ESMO (Free ESMO Whitepaper) 20thWorld Congress on Gastrointestinal Cancer in June 2018, the results from the safety lead-in of the ongoing randomized Phase 3 BEACON CRC trial showed that, at the time of analysis, the overall survival (OS) data were fully mature through 12.6 months and that the median OS had not yet been reached.

One-year overall survival rate for this cohort was 62%.
Median progression-free survival (mPFS) for patients treated with the triplet was 8 months [95% CI 5.6-9.3] and is similar between patients receiving one prior line of therapy and patients receiving two prior lines of therapy.
Confirmed overall response rate (ORR) was 48% and among the 17 patients who received only one prior line of therapy the ORR was 62%.
The triplet combination was generally well-tolerated with no unexpected toxicities. The most common grade 3 or 4 adverse events seen in at least 10% of patients were fatigue (13%), anemia (10%), increased blood creatine kinase (10%) and increased aspartate aminotransferase (10%).
The triplet combination of BRAFTOVI, MEKTOVI and cetuximab for the treatment of patients with BRAFV600E-mutant metastatic colorectal cancer is investigational and not approved by the FDA.

About Colorectal Cancer
Worldwide, colorectal cancer is the third most common type of cancer in men and the second most common in women, with approximately 1.4 million new diagnoses in 2012. Globally in 2012, approximately 694,000 deaths were attributed to colorectal cancer. [7] In the U.S. alone, an estimated 140,250 patients will be diagnosed with cancer of the colon or rectum in 2018, and approximately 50,000 are estimated to die of their disease. [8] In the U.S., BRAF mutations are estimated to occur in 10% to 15% of patients with colorectal cancer and represent a poor prognosis for these patients. [5,6,9,10] The risk of mortality in CRC patients with the BRAFV600E mutation is more than two times higher than for those with wild-type BRAF. [11] Several irinotecan plus cetuximab-containing regimens, similar to the BEACON CRC control arm, have established clinical activity benchmarks in BRAFV600E-mutant mCRC patients, whose disease has progressed after one or two prior lines of therapy, between 4% to 8% ORR, 1.8 and 2.5 months mPFS and 4 and 6 months mOS. [1-6,12]

About BEACON CRC
BEACON CRC is a randomized, open-label, global trial evaluating the efficacy and safety of BRAFTOVI, MEKTOVI and cetuximab in patients with BRAFV600E-mutant mCRC whose disease has progressed after one or two prior regimens. BEACON CRC is the first and only Phase 3 trial designed to test a BRAF/MEK combo targeted therapy in BRAFV600E-mutant mCRC. Thirty patients were treated in the safety lead-in and received the triplet combination (BRAFTOVI 300 mg daily, MEKTOVI 45 mg twice daily and cetuximab per label). Of the 30 patients, 29 had a BRAFV600E mutation. MSI-H, resulting from defective DNA mismatch repair, was detected in only 1 patient. As previously announced, the triplet combination demonstrated good tolerability, supporting initiation of the randomized portion of the trial.

The randomized portion of the BEACON CRC trial is designed to assess the efficacy of BRAFTOVI in combination with cetuximab with or without MEKTOVI compared to cetuximab and irinotecan-based therapy. Approximately 615 patients are expected to be randomized 1:1:1 to receive triplet combination, doublet combination (BRAFTOVI and cetuximab) or the control arm (irinotecan-based therapy and cetuximab). The primary endpoint of the trial is overall survival of the triplet combination compared to the control arm. Secondary endpoints address efficacy of the doublet combination compared to the control arm, and the triplet combination compared to the doublet therapy. Other secondary endpoints include PFS, ORR, duration of response, safety and tolerability. Health related quality of life data will also be assessed. The trial is being conducted at over 200 investigational sites in North America, South America, Europe and the Asia Pacific region. Patient enrollment is expected to be completed around the end of 2018.

About BRAFTOVI + MEKTOVI
BRAFTOVI (encorafenib) is an oral small molecule BRAF kinase inhibitor and MEKTOVI (binimetinib) is an oral small molecule MEK inhibitor which target key enzymes in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of proteins in this pathway has been shown to occur in many cancers including melanoma, colorectal cancer, non-small cell lung cancer, thyroid and others. In the U.S., BRAFTOVI + MEKTOVI are approved for the treatment of unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test. BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma.

Array has exclusive rights to BRAFTOVI and MEKTOVI in the U.S. and Canada. Array has granted Ono Pharmaceutical exclusive rights to commercialize both products in Japan and South Korea, Medison exclusive rights to commercialize both products in Israel and Pierre Fabre exclusive rights to commercialize both products in all other countries, including Europe, Asia and Latin America.

BRAFTOVI and MEKTOVI are not approved outside of the United States. The European Medicines Agency (EMA), the Swiss Medicines Agency (Swissmedic) and the Australian Therapeutic Goods Administration (TGA) are currently reviewing the Marketing Authorization Applications, and the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan is currently reviewing the Manufacturing and Marketing Approval Applications for BRAFTOVI and MEKTOVI.

Indications and Usage
BRAFTOVI (encorafenib) and MEKTOVI (binimetinib) are kinase inhibitors indicated for use in combination for the treatment of patients with unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test.

Limitations of Use: BRAFTOVI is not indicated for the treatment of patients with wild-type BRAF melanoma.

BRAFTOVI + MEKTOVI Important Safety Information
The information below applies to the safety of the combination of BRAFTOVI and MEKTOVI unless otherwise noted.

Warnings and Precautions
New Primary Malignancies: New primary malignancies, cutaneous and non-cutaneous malignancies can occur. In the COLUMBUS trial, cutaneous squamous cell carcinoma, including keratoacanthoma, occurred in 2.6% and basal cell carcinoma occurred in 1.6% of patients. Perform dermatologic evaluations prior to initiating treatment, every 2 months during treatment, and for up to 6 months following discontinuation of treatment. Discontinue BRAFTOVI for RAS mutation-positive non-cutaneous malignancies.

Tumor Promotion in BRAF Wild-Type Tumors: Confirm evidence of BRAFV600E or BRAFV600Kmutation prior to initiating BRAFTOVI.

Cardiomyopathy: In the COLUMBUS trial, cardiomyopathy occurred in 7% and Grade 3 left ventricular dysfunction occurred in 1.6% of patients. Cardiomyopathy resolved in 87% of patients. Assess left ventricular ejection fraction by echocardiogram or MUGA scan prior to initiating treatment, 1 month after initiating treatment, and then every 2 to 3 months during treatment. The safety has not been established in patients with a baseline ejection fraction that is either below 50% or below the institutional lower limit of normal.

Venous Thromboembolism (VTE): In the COLUMBUS trial, VTE occurred in 6% of patients, including 3.1% of patients who developed pulmonary embolism.

Hemorrhage: In the COLUMBUS trial, hemorrhage occurred in 19% of patients and ≥Grade 3 hemorrhage occurred in 3.2% of patients. Fatal intracranial hemorrhage in the setting of new or progressive brain metastases occurred in 1.6% of patients.

Ocular Toxicities: In the COLUMBUS trial, serous retinopathy occurred in 20% of patients; 8% were retinal detachment and 6% were macular edema. Symptomatic serous retinopathy occurred in 8% of patients with no cases of blindness. In patients with BRAF mutation-positive melanoma across multiple clinical trials, 0.1% of patients experienced retinal vein occlusion (RVO). Permanently discontinue MEKTOVI in patients with documented RVO. In COLUMBUS, uveitis, including iritis and iridocyclitis, was reported in 4% of patients. Assess for visual symptoms at each visit. Perform ophthalmic evaluation at regular intervals and for any visual disturbances.

Interstitial Lung Disease (ILD): ILD, including pneumonitis, occurred in 0.3% of patients with BRAFmutation-positive melanoma across multiple clinical trials. Assess new or progressive unexplained pulmonary symptoms or findings for possible ILD.

Hepatotoxicity: In the COLUMBUS trial, the incidence of Grade 3 or 4 increases in liver function laboratory tests was 6% for alanine aminotransferase (ALT) and 2.6% for aspartate aminotransferase (AST). Monitor liver laboratory tests before and during treatment and as clinically indicated.

Rhabdomyolysis: In the COLUMBUS trial, elevation of laboratory values of serum creatine phosphokinase (CPK) occurred in 58% of patients. Rhabdomyolysis was reported in 0.1% of patients with BRAF mutation-positive melanoma across multiple clinical trials. Monitor CPK periodically and as clinically indicated.

QTc Prolongation: In the COLUMBUS trial, an increase in QTcF to >500 ms was measured in 0.5% (1/192) of patients. Monitor patients who already have or who are at significant risk of developing QTc prolongation. Correct hypokalemia and hypomagnesemia prior to and during BRAFTOVI administration. Withhold, reduce dose, or permanently discontinue for QTc >500 ms.

Embryo-Fetal Toxicity: BRAFTOVI or MEKTOVI can cause fetal harm when administered to pregnant women. Nonhormonal contraceptives should be used during treatment and for at least 30 days after the final dose for patients taking BRAFTOVI + MEKTOVI.

Adverse Reactions
The most common adverse reactions (≥20%, all Grades, in the COLUMBUS trial) were: fatigue, nausea, diarrhea, vomiting, abdominal pain, arthralgia, myopathy, hyperkeratosis, rash, headache, constipation, visual impairment, serous retinopathy.

In the COLUMBUS trial, the most common laboratory abnormalities (≥20%, all Grades) included: increased creatinine, increased CPK, increased gamma glutamyl transferase, anemia, increased ALT, hyperglycemia, increased AST, and increased alkaline phosphatase.

Drug interactions
Avoid concomitant use of strong or moderate CYP3A4 inhibitors or inducers and sensitive CYP3A4 substrates with BRAFTOVI. Modify BRAFTOVI dose if concomitant use of strong or moderate CYP3A4 inhibitors cannot be avoided.

Please see full Prescribing Information for BRAFTOVI and full Prescribing Information for MEKTOVI for additional information. You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Array at 1-844-Rx-Array (1-844-792-7729).

On August 7, 2018 Array BioPharma Inc. (Nasdaq: ARRY) reported that it will report financial results for the fourth quarter and full year of fiscal 2018 and hold a conference call to discuss those results on Tuesday, August 14, 2018 (Press release, Array BioPharma, AUG 7, 2018, View Source [SID1234528515]). Ron Squarer, Chief Executive Officer, will lead the call.

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Date: Tuesday, August 14, 2018

Time: 9:00 a.m. Eastern Time

Toll-Free: (844) 464-3927

Toll: (765) 507-2598

Pass Code: 1766079

On August 7, 2018 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage pharmaceutical company focused on discovering and developing small molecule drugs that target novel and critical metabolic pathways in tumor and cancer-fighting immune cells, reported its financial results for the second quarter ended June 30, 2018 (Press release, Calithera Biosciences, AUG 7, 2018, View Source [SID1234528513]). As of June 30, 2018, cash, cash equivalents and investments totaled $152.2 million.

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"In the second quarter we continued to execute our clinical development plans for our glutaminase inhibitor and arginase inhibitor programs, while deepening our pipeline with two novel programs entering clinical development," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera. "We have advanced CB-280, a novel arginase inhibitor into development for the treatment of cystic fibrosis and we announced today our next oncometabolism drug candidate, CB-708, an orally bioavailable small molecule CD73 inhibitor."

Second Quarter 2018 and Recent Highlights

Enrolling Two Randomized Phase 2 Combination Trials of CB-839 in Combination for the Treatment of Renal Cell Carcinoma. The ENTRATA trial, a randomized double-blind placebo-controlled study of late line patients, is enrolling approximately 66 patients to receive either everolimus and CB-839 or everolimus alone. It is now expected to enroll by the fourth quarter of 2018, or early 2019. CANTATA is a randomized double-blind placebo-controlled trial comparing advanced patients treated with cabozantinib and CB-839 to patients treated with cabozantinib alone. This trial will enroll approximately 300 clear cell renal cell carcinoma patients who have previously received one or two prior lines of therapy. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for CB-839 in combination with cabozantinib for the treatment of this patient population. The trial opened in 2018 and is expected to take approximately two years to reach the primary endpoint analysis.

Presented Results of CB-839 in Combination with Capecitabine at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper). A Phase 1 Investigator sponsored clinical trial of CB-839 plus capecitabine was presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper).1 In patients with late-line colorectal cancer that had progressed on at least one prior fluoropyrimidine-containing regimen, the median PFS was 26 weeks for patients with PIK3CA mutated cancer (n=7) and 16 weeks for patients with PIK3CA wild-type cancer (n=5,p=0.058). The Phase 2 portion of this study in patients with PIK3CA mutant colorectal cancer is ongoing.

Evaluating CB-839 in Combination with Paclitaxel in Triple Negative Breast Cancer (TNBC). A Phase 2 trial evaluating CB-839 with paclitaxel in TNBC patients is ongoing. Four single arm, open label, cohorts of African American and non-African American patients are being treated in both the early and late stage settings. The primary endpoint of this trial is objective response rate and a number of predictive biomarkers are being assessed. Based on our preliminary Phase 2 clinical trial results and recent changes in the competitive landscape of TNBC, we do not plan to pursue further development of CB-839 plus paclitaxel in TNBC at this time.

Enrolling INCB001158 Clinical Trials. INCB001158 is being evaluated in multiple clinical trials for the treatment of patients with solid tumors both as a monotherapy, and in combination with immunotherapies and chemotherapy. INCB001158 is being developed as part of a collaboration and license agreement with Incyte.

Advanced Arginase Inhibitor CB-280 for the Treatment of Cystic Fibrosis. Arginase has been proposed to be critical in the pathology of cystic fibrosis by impairing production of nitric oxide. CB-280 is an orally administered small molecule inhibitor of arginase. An investigational new drug (IND) application for CB-280 with the U.S. FDA is planned for the first half of 2019.

Selected CD73 Small Molecule Inhibitor to Enter Clinical Development in 2019. The enzyme CD73 is an oncometabolism target that plays a critical role in the process of ATP conversion to adenosine. An IND application for CB-708, an orally administered small molecule inhibitor of CD73, is planned in 2019.

R&D Day Planned on October 5, 2018 in New York City. The meeting will focus on the Company’s research and development programs, including CB-280 and CB-708. To access the live audio webcast or the subsequent archived recording, visit the Investors section of the Calithera website.

Selected Second Quarter 2018 Financial Results

Cash, cash equivalents and investments totaled $152.2 million at June 30, 2018.

Revenue was $17.1 million for the three months ended June 30, 2018, compared with $7.3 million for the same period in the prior year. In the second quarter of 2018, the Company completed the manufacturing services and technology transfer under its collaboration and license agreement with Incyte, which satisfied the performance obligation under ASC 606 and as a result all remaining deferred revenue was recognized.

Research and development expenses were $17.3 million for the three months ended June 30, 2018, compared with $10.1 million for the same period in the prior year. The increase of $7.2 million was due to an increase in the CB-839 program, including for the Phase 2 CANTATA trial which opened in 2018, an increase in the INCB001158 program, including Incyte’s co-funding of development costs, an increase in the CB-280 program, including to support the IND application, as well as investment in early stage research.

General and administrative expenses were $3.5 million for the three months ended June 30, 2018, compared with $2.8 million for the same period in the prior year. The increase of $0.7 million was primarily due to increases in personnel-related costs.

Net loss from operations for the three months ended June 30, 2018 was $3.1 million, or $0.09 per share.

Conference Call Information

Calithera will host an update conference call today, August 7th at 2:00 p.m. Pacific Time/ 5:00 p.m. Eastern Time. The call can be accessed by dialing (855) 783-2599 (domestic) or (631) 485-4877 (international), and referring to conference ID 2057667. To access the live audio webcast or the subsequent archived recording, visit the Investors section of the Calithera website at www.calithera.com. The webcast will be recorded and available for replay on Calithera’s website for 30 days.

On August 7, 2018 Athersys, Inc. (NASDAQ: ATHX) reported its financial results for the three months ended June 30, 2018 (Press release, Athersys, AUG 7, 2018, View Source [SID1234528510]).

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Highlights of the second quarter of 2018 and recent events include:

Announced the completion of an expansion of our collaboration with HEALIOS K.K. ("Healios") in June 2018 to develop and commercialize additional indications for $20 million in license fees, plus potential payments and royalties, which followed a $21.1 million investment by Healios in the Company’s common stock in March 2018;

Granted to Healios a time-limited first right of negotiation for an exclusive option for a license to develop and commercialize MultiStem therapy in China for several indications;

Launched the MASTERS-2 Phase 3 registration study for ischemic stroke and enrolled initial patients into the study;

Continued to support the enrollment of Healios’ ongoing TREASURE study for ischemic stroke in Japan by providing clinical product;

Made several strategic hires, including Greg Liposky as Senior Vice President of Commercial Manufacturing to lead the execution of our manufacturing strategy;

Progressed Phase 1/2 study evaluating MultiStem therapy in acute respiratory distress syndrome (ARDS) patients, nearing enrollment completion;

Announced the award of a grant from the Medical Technology Enterprise Consortium (funded through the Department of Defense) to The University of Texas Health Science Center at Houston and Hermann Memorial Trauma Center to conduct a Phase 2 clinical trial evaluating MultiStem cell therapy for early treatment and prevention of complications after severe traumatic injury;

Recognized revenues of $19.4 million for the quarter ended June 30, 2018 and net income of $6.9 million, or $0.05 per diluted share; and

Ended the second quarter with $53.4 million of cash and cash equivalents.

"We finished the second quarter in a strong financial position, following the successful recent expansion of our partnership with Healios. We continue to explore additional partnering opportunities," commented Dr. Gil Van Bokkelen, Chairman & CEO at Athersys. "Just as importantly, we have achieved the goal of initiating our Phase 3 MASTERS-2 trial evaluating the treatment of patients that have suffered a debilitating ischemic stroke, and we are pleased to report the trial is off to a strong start.

"The recent addition of key members to the organization underscores our commitment to systematically establishing the capabilities necessary to enable us to fulfill our vision of becoming a leading biopharma company. We’re very pleased with the talented individuals and leadership that have joined the company, and we look forward to working together to achieve our goals," concluded Dr. Van Bokkelen.

Second Quarter Results

Revenues increased by $18.7 million to $19.4 million for the three months ended June 30, 2018 compared to $0.7 million for the three months ended June 30, 2017. Our revenues are derived from license fees, manufacturing-related activities for Healios, royalty and other contract revenue, and grant revenue. Our revenue from Healios increased during the second quarter of 2018 compared to the prior year second quarter by approximately $18.5 million due to the collaboration expansion in June 2018, which included several additional licensed indications.

Research and development expenses increased to $10.1 million for the three months ended June 30, 2018 from $4.6 million in the comparable period in 2017. The $5.5 million increase is primarily comprised of an increase in preclinical and clinical development costs of $4.4 million, an increase in license fees of $0.6 million, an increase in personnel costs of $0.2 million, and an increase in internal research supplies and other research costs of $0.3 million. The increase in our clinical and preclinical costs during the period is primarily a result of increased clinical product manufacturing costs, a portion of which are invoiced to Healios, technology transfer services performed on Healios’ behalf in Japan that are reimbursed to us by Healios, start-up contractual costs related to our MASTERS-2 clinical trial, and process development activities to support large-scale manufacturing.

General and administrative expenses increased to $2.4 million for the three months ended June 30, 2018 from $2.2 million in the comparable period in 2017. The $0.2 million increase was due primarily to increases in professional fees, consulting services, personnel costs and other administrative costs compared to the same period last year.

Net income for the second quarter was $6.9 million in 2018 compared to a net loss of $6.3 million in 2017. The difference of $13.2 million reflects the above variances, as well as an increase of $0.2 million in other items.

Net cash provided by operating activities was $4.4 million in the three months ended June 30, 2018 and net cash used by operating activities was $5.7 million in the three months ended June 30, 2017, reflecting the receipt of $12.5 million of license fees from our expansion with Healios, partially offset by an increase in the use of cash to fund preclinical and clinical development activities. Of the $20 million of license fees related to the June 2018 expansion with Healios, we will receive the remaining $7.5 million from Healios over the next three quarters. At June 30, 2018, we had $53.4 million in cash and cash equivalents, compared to $29.3 million at December 31, 2017.

Conference Call

Laura Campbell, Senior Vice President of Finance and William (B.J.) Lehmann, President and Chief Operating Officer, will host a conference call today to review the results as follows:

Date Tuesday, August 7th, 2018
Time 4:30 p.m. (Eastern Time)
Telephone access: U.S. and Canada 800-273-1254
Telephone access: International 973-638-3440
Access code 5144048
Live webcast www.athersys.com, under the Investors section
A replay will be available for on-demand listening shortly after the completion of the call until 11:59 PM Eastern Time on August 21st, 2018 at the aforementioned URL, or by dialing (800) 585-8367 or (855) 859-2056 in the U.S. and Canada, or from abroad (404) 537-3406, and entering access code 5144048.

About MultiStem

MultiStem cell therapy is a patented regenerative medicine product in clinical development that has shown the ability to promote tissue repair and healing in a variety of ways, such as through the production of therapeutic factors produced in response to signals of inflammation and tissue damage. MultiStem therapy’s potential for multidimensional therapeutic impact distinguishes it from traditional biopharmaceutical therapies focused on a single mechanism of benefit. The therapy represents a unique "off-the-shelf" stem cell product that can be manufactured in a scalable manner, may be stored for years in frozen form, and is administered without tissue matching or the need for immune suppression. Based upon its efficacy profile, its novel mechanisms of action, and a favorable and consistent safety profile demonstrated in clinical studies, MultiStem therapy could provide a meaningful benefit to patients, including those suffering from serious diseases and conditions with unmet medical need.

On August 7, 2018 AnaptysBio, Inc. (Nasdaq: ANAB), a clinical-stage biotechnology company developing first-in-class antibody product candidates focused on unmet medical needs in inflammation, reported operating results for the second quarter ended June 30, 2018 and provided pipeline updates (Press release, AnaptysBio, AUG 7, 2018, View Source [SID1234528509]).

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"We made significant advances during the second quarter of 2018 in the clinical development of our first-in-class wholly-owned antibody therapeutics for patients with severe inflammatory conditions," said Hamza Suria, president and chief executive officer of AnaptysBio. "We are excited to advance the clinical development of etokimab in large atopic disease markets, including our ongoing Phase 2b ATLAS trial in moderate-to-severe atopic dermatitis, our ongoing Phase 2a trial in severe eosinophilic asthma and our upcoming Phase 2 ECLIPSE trial in adult chronic rhinosinusitis with nasal polyps. Development of ANB019 in orphan diseases has been initiated with our Phase 2 GALLOP trial in generalized pustular psoriasis and upcoming Phase 2 POPLAR trial in palmoplantar pustulosis. We look forward to the five clinical efficacy readouts anticipated from our etokimab and ANB019 programs by the end of 2019, starting with our upcoming etokimab Phase 2a top-line data in eosinophilic asthma during the third quarter of 2018, as key milestones in our mission to bring novel treatments to patients with severe inflammatory diseases."

Etokimab (ANB020 Anti-IL-33 Program)

• In July 2018, etokimab (pronounced ee-toh-key-mab) was adopted as the nonproprietary name by the United States Adopted Names (USAN) Council, in consultation with the World Health Organization (WHO) International Nonproprietary Names Expert Committee, for AnaptysBio’s anti-IL-33 antibody drug candidate previously referred to as ANB020.

• In May 2018, updated data from the company’s Phase 2a trial of etokimab, AnaptysBio’s wholly-owned anti-IL-33 antibody program, in adult patients with moderate-to-severe atopic dermatitis were presented at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2018 in Munich by the principal investigator of the trial, Dr. Graham Ogg, professor of dermatology at Oxford University in Oxford, England. Key observations presented by Dr. Ogg during the aforementioned presentation included:

Biomarker data demonstrated that reduction of circulating blood eosinophil was consistent with clinical efficacy measures in this Phase 2a trial, with a maximum reduction of 40 percent at day 29 after a single dose of etokimab relative to baseline, which is aligned with genotypic studies that associate lower eosinophil counts with human IL-33 loss-of-function mutations. In addition, clinical efficacy data in this Phase 2a trial were consistent with an ex vivo pharmacodynamic assay measuring IL-33 mediated interferon-gamma release, where 98 percent inhibition was observed within 72 hours following etokimab administration and 86 percent inhibition was sustained at day 57 post-ANB020 administration, which is consistent with the pharmacodynamic activity observed using the same assay in a prior Phase 1 trial of etokimab in healthy volunteers.
A single dose of etokimab resulted in achievement of EASI-50 by all 12 patients enrolled in this trial on or before day 57 post-etokimab administration. Rapid clinical response was observed by day 15 post-etokimab administration and day 29 results exceeded the primary efficacy objective of the trial with 10 of 12 patients (83%) achieving EASI-50, of which four patients (33%) also achieved EASI-75. EASI-50 results were sustained through day 140 following single dose administration of etokimab, five of 12 patients (42%) achieved EASI-50, of which three patients (25%) also achieved EASI-75. Other atopic dermatitis efficacy endpoints, including the five-point Investigator’s Global Assessment (IGA) scale, the SCORing Atopic Dermatitis (SCORAD) scale, Dermatology Life Quality Index (DLQI) and the five-dimensional pruritus scale, demonstrated rapid and sustained single dose etokimab efficacy results in a similar manner to the aforementioned EASI results.
Etokimab was generally well-tolerated by all patients and no drug-related safety signals were observed. The most frequent adverse events reported were dizziness in 17 percent of patients post-placebo and headache in 25 percent of patients post-etokimab administration. A single serious adverse event of depression was reported on day 140 post-etokimab administration, which was consistent with the patient’s pre-trial history of depression and was deemed not drug-related.
• The company is enrolling a Phase 2b randomized, double-blinded, placebo-controlled, multi-dose study in 300 adult patients with moderate-to-severe atopic dermatitis, also referred to as the ATLAS clinical trial, to assess different dose levels and dosing frequencies of subcutaneously-administered etokimab for a 16-week treatment period followed by an eight-week follow-up period, with data expected in the second half of 2019. Sixty patients are being randomized into each of the five arms in the ATLAS trial where dosing will occur as follows: (i) initial 600mg loading dose followed by 300mg monthly doses of etokimab, (ii) initial 300mg loading dose followed by 150mg monthly doses of etokimab, (iii) initial 300mg loading dose followed by 150mg doses of etokimab every eight weeks, (iv) monthly 20mg doses of etokimab and (v) monthly doses of placebo.

• AnaptysBio expects to report top-line efficacy and safety data, including improvement in Forced Expiratory Volume in One Second (FEV1), from its ongoing double-blinded, placebo-controlled severe eosinophilic asthma trial Phase 2a trial, where approximately 24 adult severe eosinophilic asthma patients are treated with a 300mg intravenous single dose of etokimab versus placebo, each in combination with inhaled corticosteroids and long-acting beta agonists as background therapy, in the third quarter of 2018.

• The Company has expanded development of etokimab into adult chronic rhinosinusitis with nasal polyps (CRSwNP), which is a debilitating atopic disorder associated with elevated IL-33 pathway signaling, affecting approximately 1.3 million adults in the U.S., and AnaptysBio estimates approximately 400,000 of these patients are inadequately controlled with standard-of-care. The Company plans to initiate a randomized, placebo-controlled Phase 2 trial, also referred to as the ECLIPSE trial, in approximately 100 adult CRSwNP patients treated with two different multi-dosing frequencies of subcutaneously-administered etokimab or placebo, each in combination with mometasone furoate nasal spray as background therapy, for a treatment period of 16 weeks followed by an eight-week follow-up period. The Company plans to initiate the ECLIPSE trial by the end of 2018, and anticipates top-line data will be available in the second half of 2019.

• As a result of market assessment regarding the adoption of the peanut oral food challenge in future commercial usage of etokimab in peanut allergy patients, AnaptysBio has decided to deprioritize further company-sponsored clinical development of etokimab in moderate-to-severe baseline adult peanut allergy patients. At this time, AnaptysBio does not intend to utilize its clinical development resources to pursue a Phase 2b clinical trial of etokimab in peanut allergy, however the Company may pursue potential investigator-sponsored trials related to this indication.

ANB019 (Anti-IL-36 Receptor Program)

• Data from the company’s Phase 1 healthy volunteer trial of ANB019, its wholly-owned anti-interleukin-36 receptor, or IL-36R therapeutic antibody, were presented during May in a poster session at the EAACI Congress 2018 in Munich. In the double-blind, placebo-controlled healthy volunteer Phase 1 trial, 36 subjects were administered a single subcutaneous or intravenous dose of ANB019 ranging between 10 mg and 750 mg, 18 subjects were administered multiple ascending doses of ANB019 intravenously ranging between 40 mg and 300 mg weekly for four consecutive weeks and 18 subjects were dosed with placebo. ANB019 was well-tolerated by all subjects and no dose-limiting toxicities were observed. The most frequent treatment-emergent adverse events observed in the single ascending dose cohorts were upper respiratory tract infections in 10 of 36 (28%) subjects dosed with ANB019 versus six of 12 (50%) subjects dosed with placebo, and headache in 10 of 36 (28%) subjects dosed with ANB019 versus three of 12 (25%) subjects dosed with placebo. In the multiple ascending dose cohorts, the most frequent treatment-emerging adverse events observed were headache in seven of 18 (39%) subjects dosed with ANB019 versus one of six (17%) subjects dosed with placebo. No serious adverse events were reported among any subjects in the trial. The in vivo half-life of ANB019 was approximately 28 days for both subcutaneous and intravenous routes of administration, with bioavailability of approximately 90 percent. A single dose of ANB019 at certain dose levels was able to completely suppress IL-36 cytokine function for 85 days, as measured by IL-36 cytokine-mediated release of IL-8 using an ex vivo pharmacodynamic assay. The favorable safety, pharmacokinetics and pharmacodynamic properties of ANB019 demonstrated by this Phase 1 trial support advancement of ANB019 into Phase 2 studies for GPP and PPP.

• AnaptysBio has initiated a 10-patient open-label Phase 2 trial of ANB019 in GPP, also known as the GALLOP trial and top-line data are anticipated by early 2019. Patients are dosed with a 750mg intravenous loading dose of ANB019 upon enrollment, followed by 100mg subcutaneously-administered monthly doses of ANB019 for a treatment period of up to 16 weeks post enrollment and followed an eight-week follow-up period. The company plans to initiate a placebo-controlled 50-patient multi-dose Phase 2 trial in PPP, also known as the POPLAR trial, where top line data is anticipated in the second half of 2019.

Second Quarter Financial Results

• Cash, cash equivalents and investments totaled $300.6 million as of June 30, 2018 compared to $324.3 million as of December 31, 2017, for a decrease of $23.7 million. The decrease primarily relates to operating cash outflow for clinical and manufacturing related expenses, as well as personnel costs.

• Research and development expenses were $10.6 million for the three months ended June 30, 2018, as compared to $7.2 million for the three months ended June 30, 2017. The increase was primarily due to continued advancement of the Company’s ANB020 and ANB019 clinical programs and additional personnel-related expenses, including share based compensation, as well as the recognition of lower research and development tax incentives during the three months ended June 30, 2018.

• General and administrative expenses were $3.8 million for the three months ended June 30, 2018, as compared to $2.4 million for the three months ended June 30, 2017. The increase was primarily attributable to additional personnel-related expenses, including share based compensation, to support the Company’s growth.

Financial Guidance

AnaptysBio expects that its cash, cash equivalents and investments will fund its current operating plan through the end of 2019.

About Etokimab

Etokimab, previously referred to as ANB020, is an antibody that potently binds and inhibits the activity of interleukin-33, or IL-33, a pro-inflammatory cytokine that multiple studies have indicated is a central mediator of atopic diseases, which we believe is broadly applicable to the treatment of atopic inflammatory disorders, such as moderate-to-severe adult atopic dermatitis, severe adult eosinophilic asthma, adult CRSwNP and potentially other allergic conditions. Following completion of a healthy volunteer Phase 1 trial of etokimab, AnaptysBio has continued clinical development of etokimab into a Phase 2a trial for moderate-to-severe adult atopic dermatitis and a 24-patient placebo-controlled Phase 2a trial in severe adult eosinophilic asthma patients where top-line data are anticipated in the third quarter 2018. AnaptysBio is enrolling its ATLAS trial, a placebo-controlled multi-dose Phase 2b clinical trial of etokimab in 300 moderate-to-severe adult atopic dermatitis patients where data is anticipated in the second half of 2019. AnaptysBio also plans to initiate its ECLIPSE trial, a randomized, placebo-controlled Phase 2 trial of etokimab in approximately 100 adult patients with CRSwNP by the end of 2018 with data anticipated in the second half of 2019.

About ANB019

ANB019 is an antibody that inhibits the function of the interleukin-36-receptor, or IL-36R, which AnaptysBio plans to initially develop as a potential first-in-class therapy for patients suffering from generalized pustular psoriasis (GPP) and palmoplantar pustulosis (PPP). AnaptysBio conducted a Phase 1 clinical trial in healthy volunteers, where 54 subjects are dosed with ANB019 and 18 are dosed with placebo in single and multi-dose cohorts at various subcutaneous and intravenously administered dose levels. In May 2018, AnaptysBio presented data from this Phase 1 clinical trial, which demonstrated favorable safety, pharmacokinetics and pharmacodynamic properties that support advancement of ANB019 into Phase 2 studies. AnaptysBio is enrolling its GALLOP trial, a Phase 2 study of ANB019 in GPP where data is anticipated in early 2019, and plans to initiate its POPLAR trial, a Phase 2 study in PPP in 2018 where data is anticipated in the second half of 2019.