On January 26, 2018 Astellas Pharma Inc. (TSE: 4503, President and CEO: Yoshihiko Hatanaka, "Astellas") reported new data to be presented at the 2018 Genitourinary Cancers Symposium of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (ASCO GU) taking place on February 8-10 in San Francisco (Press release, Astellas, 26 26, 2018, View Source [SID1234523593]). Among the data being presented are findings for men with non-metastatic Castration-Resistant Prostate Cancer (CRPC) taking enzalutamide*; and for patients with locally advanced or metastatic urothelial cancer taking enfortumab vedotin**, an investigational antibodydrug conjugate (ADC).

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"We are poised to announce our largest presence to date at this year’s ASCO (Free ASCO Whitepaper) GU meeting," said Steven Benner, M.D., senior vice president and global therapeutic area head, Oncology Development, Astellas. "We’re pleased to showcase additional work in our oncology franchise, investigating new indications and uses where possible for patients through expanded indications and tumor types in areas of high unmet need."

The following abstract will be featured during an oral presentation session for enzalutamide:

Title: PROSPER: A phase 3, randomized, double-blind, placebo (PBO)- controlled study of enzalutamide (ENZA) in men with nonmetastatic castration-resistant prostate cancer (M0 CRPC)

Presenter: Maha Hussain, M.D.

Oral Presentation Abstract Session A: Prostate Cancer; Abstract Number: 3
Session Date/Time: Thursday, February 8, 1:00 p.m.- 2:30 p.m. PST
In addition to the oral presentation, the following six abstracts will be presented during the poster sessions for enzalutamide:

Title: Hepatic effects assessed by review of safety data in enzalutamide castration-resistant prostate cancer (CRPC) trials

Lead Author: Tomasz M. Beer, M.D.

Poster Session A: Prostate Cancer; Abstract Number: 199
Session Date/Time: Thursday, February 8, 11:30 a.m.-1:00 p.m.; 5:15 p.m.- 6:15 p.m. PST
Title: Impact of enzalutamide (ENZA) vs. bicalutamide (BIC) on healthrelated quality of life (HRQoL) of patients (pts) with castration-resistant prostate cancer (CRPC): STRIVE study

Lead Author: Raoul Concepcion, M.D.

Poster Session A: Prostate Cancer; Abstract Number: 234
Session Date/Time: Thursday, February 8, 11:30 a.m.-1:00 p.m.; 5:15 p.m. – 6:15 p.m. PST
Title: Comparison of enzalutamide and bicalutamide in patients with nonmetastatic castration resistant prostate cancer: Number needed to treat to achieve one additional patient free of clinical progression events

Lead Author: Lawrence Ivan Karsh, M.D.

Poster Session A: Prostate Cancer Abstract Number: 228
Session Date/Time: Thursday, February 8, 11:30 a.m.-1:00 p.m.; 5:15 p.m.- 6:15 p.m. PST
Title: Treatment duration and utilization patterns in metastatic castrationresistant prostate cancer patients receiving enzalutamide or abiraterone acetate

Lead Author: Vahan Kassabian, M.D.

Poster Session A: Prostate Cancer; Abstract Number: 229
Session Date/Time: Thursday, February 8, 11:30 a.m.-1:00 p.m.; 5:15 p.m.- 6:15 p.m. PST
Title: Health care resource utilization and costs in metastatic castrationresistant prostate cancer patients treated with enzalutamide or abiraterone acetate

Lead Author: Vahan Kassabian, M.D.

Poster Session A: Prostate Cancer; Abstract Number: 232
Session Date/Time: Thursday, February 8, 11:30 a.m.-1:00 p.m.; 5:15 p.m.- 6:15 p.m. PST
Title: Safety of continued administration of enzalutamide in patients with prostate cancer who showed benefit from prior exposure: A Phase 2 openlabel extension study

Lead Author: Elaine Tat Lam, M.D.

Poster Session B: Prostate Cancer, Urothelial Carcinoma, and Penile, Urethral, and Testicular Cancers; Abstract Number: 303
Session Date/Time: Friday, February 9, 12:15 p.m.-1:45 p.m.; 6 p.m. – 7 p.m. PST
Astellas will present the following three abstracts during poster sessions for enfortumab vedotin, which include updated Phase 1 data in metastatic urothelial cancer patients with prior CPI treatment and trials in progress (TIP) for the EV-201 and EV-103 studies.

Title: Enfortumab vedotin (EV) in patients (Pts) with metastatic urothelial carcinoma (mUC) with prior checkpoint inhibitor (CPI) failure: A prospective cohort of an ongoing phase 1 study

Lead Author: Daniel P. Petrylak, M.D.

Poster Session B: Prostate Cancer, Urothelial Carcinoma, and Penile, Urethral, and Testicular Cancers; Abstract Number 431
Session Date/Time: Friday, February 9, 12:15 p.m.-1:45 p.m.; 6:00 p.m.-7:00 p.m. PST
Title: EV-201 study: A single-arm, open-label, multicenter study of enfortumab vedotin for treatment of patients with locally advanced or metastatic urothelial cancer who previously received immune checkpoint inhibitor therapy

Lead Author: Jonathan E. Rosenberg, M.D.

Trials in Progress Poster Session B: Prostate Cancer, Urothelial Carcinoma, and Penile, Urethral, and Testicular Cancers; Abstract Number TPS542
Session Date/Time: Friday, February 9, 12:15 p.m.-1:45 p.m.; 6:00 p.m.-7:00 p.m. PST
Title: EV-103 study: A phase 1b dose-escalation and dose-expansion study of enfortumab vedotin in combination with immune checkpoint inhibitor (CPI) therapy for treatment of patients with locally advanced or metastatic urothelial cancer

Lead Author: Christopher J. Hoimes, D.O.

Trials in Progress Poster Session B: Prostate Cancer, Urothelial Carcinoma, and Penile, Urethral, and Testicular Cancers; Abstract Number TPS532
Session Date/Time: Friday, February 9, 12:15 p.m.-1:45 p.m.; 6:00 p.m.-7:00 p.m. PST
*Enzalutamide is developed through a collaboration between Pfizer and Astellas and commercialized under the brand name XTANDI.

**Enfortumab vedotin is developed through a collaboration between Seattle Genetics and Astellas.

About Enfortumab Vedotin

Enfortumab vedotin is an investigational Antibody-Drug Conjugate (ADC), composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent, monomethyl auristatin E (MMAE), using Seattle Genetics’ proprietary, industryleading linker technology. Enfortumab vedotin targets Nectin-4, a cell adhesion molecule identified as an ADC target by Astellas, which is expressed on many solid tumors.

About XTANDI (enzalutamide) capsules
XTANDI (enzalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with metastatic castration-resistant prostate cancer.

Important Safety Information

Contraindications
XTANDI is not indicated for women. XTANDI can cause fetal harm and potential loss of pregnancy.

Warnings and Precautions
Seizure occurred in 0.5% of patients receiving XTANDI in clinical studies. In a study of patients with predisposing factors, seizures were reported in 2.2% of patients. See section 5.1 of the Prescribing Information for the list of predisposing factors. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES)
In post approval use, there have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder which can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Adverse Reactions
The most common adverse reactions (≥ 10%) that occurred more commonly (≥ 2% over placebo) in the XTANDI patients from the two placebo-controlled clinical trials were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/vertigo. In the bicalutamide-controlled study of chemotherapy-naïve patients, the most common adverse reactions (≥ 10%) reported in XTANDI patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, upper respiratory tract infection, diarrhea, and weight loss.

In the placebo-controlled study of patients taking XTANDI who previously received docetaxel, Grade 3 and higher adverse reactions were reported among 47% of XTANDI patients and 53% of placebo patients. Discontinuations due to adverse events were reported for 16% of XTANDI patients and 18% of placebo patients. In the placebo-controlled study of chemotherapy-naïve patients, Grade 3-4 adverse reactions were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to adverse events were reported for 6% of both study groups. In the bicalutamide-controlled study of chemotherapy-naïve patients, Grade 3-4 adverse reactions were reported in 38.8% of XTANDI patients and 37.6% of bicalutamide patients. Discontinuations due to adverse events were reported for 7.6% of XTANDI patients and 6.3% of bicalutamide patients.

Lab Abnormalities: In the two placebo-controlled trials, Grade 1-4 neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and 6% of placebo patients (0.5% Grade 3-4). Grade 1-4 thrombocytopenia occurred in 6% of XTANDI patients (0.3% Grade 3-4) and 5% of placebo patients (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of XTANDI patients (0.2% Grade 3-4) and 16% of placebo patients (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of XTANDI patients (0.1% Grade 3-4) and 2% of placebo patients (no Grade 3-4).

Infections: In the study of patients taking XTANDI who previously received docetaxel, 1% of XTANDI patients compared to 0.3% of placebo patients died from infections or sepsis. In the study of chemotherapy-naïve patients, 1 patient in each treatment group (0.1%) had an infection resulting in death.

Falls (including fall-related injuries) occurred in 9% of XTANDI patients and 4% of placebo patients in the two placebo-controlled trials. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in XTANDI patients, and included non-pathologic fractures, joint injuries, and hematomas.

Hypertension occurred in 11% of XTANDI patients and 4% of placebo patients in the two placebo-controlled trials. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of patients in each arm.

Drug Interactions
Effect of Other Drugs on XTANDI Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI.

Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI.

Effect of XTANDI on Other Drugs Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

Please see Full Prescribing Information for additional safety information.

On January 26, 2018 Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to improve the survival and quality of life of cancer patients, reported that a poster highlighting the synergistic effects of duvelisib in combination with immune checkpoint or co-stimulatory antibodies in preclinical models of B cell lymphoma was presented at ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium being held January 25-27, 2018 in San Francisco (Press release, Verastem, JAN 26, 2018, View Source;p=RssLanding&cat=news&id=2328722 [SID1234523588]). Duvelisib is a first-in-class oral dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma that is currently being developed for the treatment of relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (FL). In addition, duvelisib is being studied in other hematologic malignancies including peripheral T cell lymphoma (PTCL).

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"In patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma and follicular lymphoma, oral duvelisib monotherapy has demonstrated efficacy, along with a consistent and manageable safety profile. However, emerging data suggest that some aggressive lymphomas will likely require combination therapy to improve clinical outcomes," said Jonathan Pachter, PhD, Chief Scientific Officer of Verastem. "Our research presented this year at ASCO (Free ASCO Whitepaper)-SITC indicates that the dual PI3K-delta/PI3K-gamma inhibitory activity of duvelisib enables duvelisib to reduce both T-regulatory (Treg) and myeloid immunosuppressive cells in a murine A20 B cell lymphoma model. As a result of these beneficial changes within the tumor microenvironment, we observed a striking enhancement by duvelisib of the anti-tumor efficacy of immune checkpoint or co-stimulatory antibodies in this preclinical B cell lymphoma model. These data support further exploration of duvelisib in combination with immunotherapeutic agents for the treatment of aggressive lymphomas."

Oral duvelisib is the first PI3K inhibitor to show efficacy as an oral monotherapy in a randomized Phase 3 study in patients with relapsed or refractory CLL/SLL (the DUO study). In the Phase 2 DYNAMO study, duvelisib achieved meaningful clinical activity in patients diagnosed with follicular lymphoma (FL), small lymphocytic lymphoma (SLL), or marginal zone lymphoma (MZL) whose disease is refractory to rituximab and to a chemotherapy regimen or radioimmunotherapy. Verastem plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) during the first quarter of 2018 requesting full approval of duvelisib for the treatment of patients with relapsed or refractory CLL/SLL and accelerated approval for the treatment of patients with relapsed or refractory follicular lymphoma (FL).

Details for the poster presentation at ASCO (Free ASCO Whitepaper)-SITC 2018 are:

Title: Dual PI3K-δ,γ inhibitor duvelisib reduces immunosuppressive Tregs and myeloid cells enhancing efficacy of checkpoint and co-stimulatory antibodies in a B cell lymphoma model
Session: Developmental Therapeutics – Poster Session B
Abstract #: 33
Location: Golden Gate Hall – B2 Level – Poster Board D1
Date and time: Friday, January 26, 2018; 11:30am to 1:00pm PT and 5:30 to 6:30pm PT
Summary: Prior published research has shown that PI3K-delta inhibition reduces immunosuppressive Tregs and PI3K-gamma inhibition reduces immunosuppressive myeloid cells. As a result, it was hypothesized that duvelisib may augment the efficacy of immune checkpoint or co-stimulatory antibodies. For this study, Verastem researchers administered duvelisib alone, anti-PD-1 alone, anti-OX40 alone, duvelisib + anti-PD-1, duvelisib + anti-OX40, or vehicle control to mice bearing syngeneic A20 B cell lymphoma tumors.

Duvelisib alone, anti-PD-1 alone and anti-OX40 alone each induced tumor growth delay. When duvelisib and anti-PD-1 were combined, strong anti-tumor synergy was observed. When duvelisib and anti-OX40 were combined, tumor regression was observed which correlated with strong reduction of tumor Tregs, M2 macrophages and myeloid-derived suppressor cells. Immune memory was also assessed by injecting mice that had become tumor free with A20 cells following anti-OX40 alone or duvelisib + anti-OX40 with no further treatment. The mice that had received anti-OX40 alone grew new tumors upon A20 re-challenge, however, all mice that had received duvelisib + anti-OX40 did not grow tumors upon re-challenge and showed elevated memory T cells in blood and spleen. These findings indicate that treatment with duvelisib + anti-OX40 established immune memory. The dual inhibition of PI3K-δ and PI3K-γ appears to make duvelisib effective in reducing both lymphoid and myeloid immuno-suppressive populations, consistent with prior data suggesting that PI3K-δ inhibition reduces immunosuppressive Tregs, whereas PI3K-γ inhibition reduces immunosuppressive myeloid cells. We believe these results showing that dual PI3K-δ and PI3K-γ inhibition can enhance the anti-tumor efficacy of immune checkpoint and co-stimulatory antibodies which potentially support the clinical exploration of duvelisib in combination with these agents.

A copy of the poster presentation will be available here following the conclusion of the poster sessions.

About the Tumor Microenvironment

The tumor microenvironment encompasses various cellular populations and extracellular matrices within the tumor or cancer niche that support cancer cell survival. This includes immunosuppressive cell populations such as regulatory T-cells, myeloid-derived suppressor cells, M2 TAMS, as well as tumor-associated fibroblasts and extracellular matrix proteins which can hamper the entry and therapeutic benefit of cytotoxic immune cells and anti-cancer drugs. In addition to targeting the proliferative and survival signaling of cancer cells, Verastem’s compounds duvelisib and defactinib target the tumor microenvironment as a mechanism of action to potentially improve a patient’s response to therapy.

About Duvelisib

Duvelisib is a first-in-class investigational, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells and T-cells. PI3K signaling may lead to the proliferation of malignant B- and T-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 Duvelisib is currently being evaluated in late- and mid-stage extension trials, including DUO, a randomized, Phase 3 monotherapy study in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL),4 and DYNAMO, a single-arm, Phase 2 monotherapy study in patients with refractory indolent non-Hodgkin lymphoma (iNHL).5 Both DUO and DYNAMO achieved their primary endpoints and Verastem intends to submit a New Drug Application (NDA) requesting the full approval of duvelisib for the treatment of patients with relapsed or refractory CLL/SLL, and accelerated approval for the treatment of patients with relapsed or refractory follicular lymphoma (FL). Duvelisib is also being developed by Verastem for the treatment of peripheral T-cell lymphoma (PTCL), and is being investigated in combination with other agents through investigator-sponsored studies.6 Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.

On January 26, 2018 Eli Lilly and Company (NYSE: LLY) reported that it will present at the Leerink Partners Global Healthcare Conference on Thursday, February 15, 2018 (Press release, Eli Lilly, JAN 26, 2018, View Source [SID1234523585]). Jan Lundberg, Ph.D., executive vice president for science and technology and president of Lilly Research Laboratories, and Dan Skovronsky, M.D., Ph.D., senior vice president of clinical and product development at Lilly, will participate in a fireside chat at 10:30 a.m., Eastern Time.

A live audio webcast will be available on the "Webcasts & Presentations" section of Lilly’s investor website at View Source A replay of the fireside chat will be available for approximately 90 days.

On January 26, 2018 AbbVie (NYSE:ABBV) reported financial results for the fourth quarter ended December 31, 2017 (Press release, AbbVie, JAN 26, 2018, View Source [SID1234523584]).

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"2017 reflects another year of top-tier performance, demonstrating the strong momentum in our business," said Richard A. Gonzalez, chairman and chief executive officer, AbbVie. "Our guidance for 2018 underscores our confidence in our ability to continue to deliver industry-leading performance. This is an exciting time for AbbVie — we are poised to launch a number of differentiated products over the next 12 to 18 months that will fuel significant growth in the coming years. We remain committed to delivering on our long-term strategic vision for AbbVie.

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Fourth-Quarter Results

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Worldwide net revenues were $7.739 billion in the fourth quarter, up 13.9 percent year-over-year on a GAAP basis. On an operational basis, adjusted net revenues increased 12.6 percent, excluding a 1.5 percent favorable impact from foreign exchange.

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Global HUMIRA sales increased 14.0 percent on a reported basis, or 12.3 percent operationally, excluding a 1.7 percent favorable impact from foreign exchange. In the U.S., HUMIRA sales grew 15.1 percent in the quarter. Internationally, HUMIRA sales grew 6.5 percent, excluding a 5.2 percent favorable impact from foreign exchange.

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Fourth-quarter global IMBRUVICA net revenues were $708 million, with U.S. sales of $585 million and international profit sharing of $123 million for the quarter, reflecting growth of 38.7 percent.

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On a GAAP basis, the gross margin ratio in the fourth quarter was 70.5 percent. The adjusted gross margin ratio was 79.0 percent.

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On a GAAP basis, selling, general and administrative expense was 25.2 percent of net revenues. The adjusted SG&A expense was 21.2 percent of net revenues.

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On a GAAP basis, research and development expense was 18.1 percent of net revenues. The adjusted R&D expense was 17.1 percent, reflecting funding actions supporting all stages of our pipeline.

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On a GAAP basis, the operating margin in the fourth quarter was 23.2 percent. The adjusted operating margin was 40.7 percent.

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On a GAAP basis, net interest expense was $252 million.

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Financial results for 2017 reflected a net charge of $0.77 per diluted share related to the December 2017 enactment of the Tax Cuts and Jobs Act. The net charge included the one-time impact of approximately
$4.5 billion for mandatory taxation on previously unrepatriated earnings, partially offset by the revaluation of tax-related balance sheet items. These amounts have been treated as specified and excluded from adjusted diluted EPS. On a GAAP basis, the tax rate in the quarter was 95.6 percent. The adjusted tax rate was 18.9 percent.

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Diluted EPS in the fourth quarter was $0.03 on a GAAP basis. Adjusted diluted EPS, excluding specified items, was $1.48, up 23.3 percent.

Key Events from the Fourth Quarter

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AbbVie announced positive top-line results from the Phase 3 SELECT-MONOTHERAPY clinical trial evaluating upadacitinib (ABT-494) as a monotherapy treatment in patients with moderate to severe rheumatoid arthritis who did not adequately respond to treatment with methotrexate. Results showed that after 14 weeks of treatment, both once-daily doses of upadacitinib (15 mg and 30 mg) met the study’s primary endpoints of ACR20 and low disease activity versus continuing prior stable methotrexate therapy. Both doses also achieved all ranked and all key secondary endpoints. The safety profile of upadacitinib was consistent with previously reported Phase 3 SELECT clinical trials and Phase 2 studies, and no new safety signals were detected. AbbVie expects data from two additional registrational studies in the first half of 2018, supporting regulatory submissions in the second half of 2

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Key Events from the Fourth Quarter (continued)

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AbbVie announced the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for upadacitinib in adult patients with moderate to severe atopic dermatitis who are candidates for systemic therapy, supported by positive Phase 2b results. The Phase 3 clinical program for upadacitinib in atopic dermatitis is expected to begin in the first half of 2018.

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AbbVie announced top-line results from the IMMhance study, the fourth pivotal clinical trial evaluating risankizumab, an investigational interleukin-23 (IL-23) inhibitor, for the treatment of patients with moderate to severe plaque psoriasis. Results showed that risankizumab met all co-primary and ranked secondary endpoints in the study. At week 16, nearly half (47 percent) of patients receiving risankizumab achieved complete skin clearance (PASI 100) versus placebo (1 percent), and static Physician Global Assessment (sPGA) score of clear or almost clear skin was achieved by 84 percent of risankizumab patients compared to 7 percent of placebo patients. Among patients who achieved clear or almost clear skin at week 28, 87 percent of patients maintained this response at one year, compared to 61 percent who were switched to placebo at week 28. Risankizumab’s safety profile in IMMhance was consistent with previously reported Phase 3 clinical trials, with no new safety signals detected across the Phase 3 program. The company plans to submit its applications for regulatory approval in the first half of 2018. Risankizumab is being developed in collaboration with Boehringer Ingelheim.

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AbbVie presented results from the Phase 3 MURANO study of VENCLEXTA/VENCLYXTO (venetoclax) in combination with Rituxan at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Results show that patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) achieved significantly prolonged median progression-free survival (PFS) with VENCLEXTA in combination with Rituxan compared with bendamustine in combination with Rituxan. Investigator-assessed twenty-four month PFS estimates were 84.9 percent and 36.3 percent, respectively, with independent review committee (IRC)-assessed PFS showing similar results. Also in the trial, 83.5 percent of patients achieved peripheral blood minimal residual disease (MRD)-negativity with VENCLEXTA in combination with Rituxan, compared to 23.1 percent with bendamustine in combination with Rituxan. At the time of the analysis, safety data were consistent with the known safety profiles of the medicines. Regulatory applications were recently submitted for VENCLEXTA in combination with Rituxan for treatment of patients with R/R CLL. VENCLEXTA is being developed by AbbVie and Genentech, a member of the Roche Group.

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AbbVie presented new and updated IMBRUVICA (ibrutinib) data at the ASH (Free ASH Whitepaper) meeting, including pooled analysis results of the longest follow-up data to-date in Bruton’s tyrosine kinase (BTK) inhibition for R/R mantle cell lymphoma (MCL) patients treated with IMBRUVICA, demonstrating that, at three years, 45 percent of patients were able to achieve overall survival (OS) and 26 percent had PFS. AbbVie also presented new three-year follow-up data from the RESONATE-2 study (PCYC-1115/1116), which found that previously-untreated CLL/SLL patients reported sustained improvements in measures of well-being with IMBRUVICA versus chemotherapy with chlorambucil. At 30 months, IMBRUVICA was also associated with a greater PFS rate of 85 percent versus chlorambucil, which had a PFS rate of 28 percent. IMBRUVICA is jointly developed and commercialized with Janssen Biotech, Inc.

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AbbVie announced the Phase 3 iNNOVATE trial evaluating IMBRUVICA in combination with Rituxan in patients with treatment-naïve and previously-treated Waldenström’s macroglobulinemia successfully met its primary endpoint and demonstrated improvement of PFS compared to Rituxan alone. The Independent Data Monitoring Committee recommended that the study be unblinded based on the positive outcome from the pre-specified interim analysis data. The company expects to submit these data for label augmentation in 2018.

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Key Events from the Fourth Quarter (continued)

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At the American Society for Reproductive Medicine Scientific Congress & Expo (ASRM), AbbVie, in cooperation with Neurocrine Biosciences, presented detailed results from two replicate Phase 3 extension studies evaluating the long-term efficacy and safety of elagolix, an investigational, orally administered gonadotropin-releasing hormone (GnRH) antagonist, being evaluated for the management of endometriosis with associated pain. In the extension studies, elagolix demonstrated sustained reduction in average monthly menstrual pelvic pain and non-menstrual pelvic pain in women through the 12-month treatment period. The safety and tolerability of elagolix was consistent with the anticipated effects of reduced estradiol levels and no new safety concerns were identified with elagolix use for the 12-month treatment period. Elagolix is currently under priority regulatory review for the management of endometriosis with associated pain.

Full-Year 2018 Outlook, Including Impact of U.S. Tax Reform

GAAP diluted EPS for the full-year 2018 is expected to be between $6.45 and $6.55.

AbbVie is raising its previously announced adjusted EPS guidance range for the full-year 2018 from $6.37 to $6.57 to $7.33 to $7.43 to reflect the impact of U.S. tax reform and stronger operating performance. The midpoint of this guidance reflects year-over-year growth of 32 percent, more than half of which is driven by growth in the underlying business. Relative to the previously issued 2018 guidance provided in October 2017, this guidance includes an increase of $0.08 as a result of stronger operating dynamics.

AbbVie’s adjusted EPS guidance range reflects an effective tax rate of approximately 9 percent in 2018. In 2018, AbbVie will experience a one-time net tax benefit related to the timing of the phase in of provisions of the new legislation on certain subsidiaries. This benefit has been excluded from the adjusted EPS guidance, and included in the GAAP guidance range.

AbbVie anticipates the company’s adjusted effective tax rate to increase to 13 percent over the next five years as a result of increased domestic income and investment.

Increased U.S. Investments

Over the next five years, AbbVie plans to invest approximately $2.5 billion in capital projects in the U.S. and the company is currently evaluating additional expansion of its U.S. facilities. Also, in 2018, the company plans to make a one-time charitable contribution of approximately $350 million to select not-for-profit organizations based in the United States. The company also plans to accelerate pension funding by $750 million, as well as enhance non-executive employee compensation.

Provisional Estimates of the Impact of U.S. Tax Reform

Financial results for 2017 reflect provisional amounts related to the December 2017 enactment of the Tax Cuts and Jobs Act. These provisional estimates are based on AbbVie’s initial analysis and current interpretation of the legislation. Given the complexity of the legislation, anticipated guidance from the U.S. Treasury, and the potential for additional guidance from the Securities and Exchange Commission (SEC) or the Financial Accounting Standards Board, these estimates may be adjusted during 2018.

On January 25, 2019 Alligator Bioscience (Nasdaq Stockholm: ATORX), a biotechnology company developing antibody-based pharmaceuticals for tumor-directed immunotherapy, reported that it has appointed Theradex Oncology, a global contract research organization ("CRO") with extensive expertise in oncology clinical development, as CRO for the planned phase I study of ATOR-1015 for the treatment of metastatic cancer (Press release, Alligator Bioscience, JAN 25, 2018, View Source [SID1234538681]). The study is expected to commence in the second half of 2018.

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The upcoming clinical phase I study with ATOR-1015 is a first-in-human dose escalation study in patients with metastatic cancer. The study will be conducted at five sites in Sweden and Denmark.

"Engaging Theradex is a key step towards starting our clinical phase I study with ATOR-1015 later this year", said Per Norlén, CEO of Alligator Bioscience. "We have worked previously with Theradex on the ADC-1013 clinical phase I trial and, based on their robust delivery and extensive expertise in clinical oncology research, we are confident in their ability to assist us in executing high-quality studies and we look forward to continuing our successful collaboration".

ATOR-1015 is a first-in-class bispecific antibody that targets CTLA-4 and OX40 and was created with Alligator’s unique bispecific technology. Alligator has advanced ATOR-1015 through preclinical development and is now preparing for the start of a clinical phase I study. Production of clinical trial material has already been completed and the final clinical trial authorization ("CTA") enabling activities required for study initiation will be completed in H1 2018.

For further information, please contact:
Cecilia Hofvander, Director Investor Relations & Communications
Phone +46 46 286 44 95
E-mail: [email protected].

The information was submitted for publication, through the agency of the contact person set out above, at 08:30 a.m. CET on 25 January 2018.

About ATOR-1015
ATOR-1015 is a next generation CTLA-4 bispecific antibody developed for tumor-directed immunotherapy with increased capability of regulatory T-cell depletion. It is fully owned by Alligator. ATOR-1015 binds to two different immune receptors: the checkpoint receptor CTLA-4 and the co-stimulatory receptor OX40. The immune activation is increased in areas where both target molecules are expressed at high levels, notably in the tumor microenvironment, which is believed to reduce adverse immune reactions.