On February 10, 2018 AVEO Oncology (NASDAQ: AVEO) and EUSA Pharma reported the presentation of preliminary results from the Phase 2 portion of the TiNivo study, a Phase 1b/2 multicenter trial of oral (PO) tivozanib (FOTIVDA) in combination with intravenous (IV) nivolumab (OPDIVO, Bristol-Myers Squibb), an immune checkpoint, or PD-1, inhibitor, for the treatment of metastatic renal cell carcinoma (mRCC) (Press release, AVEO, FEB 10, 2018, View Source;p=RssLanding&cat=news&id=2331694 [SID1234523891]). The results were presented today at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s Genitourinary Cancers Symposium (ASCO GU), in a poster presentation titled "Tivozanib combined with nivolumab: Phase Ib/II study in metastatic renal cell carcinoma (mRCC)" (Abstract 618). A copy of the presentation is available at www.aveooncology.com or further information can be obtained via EUSA Pharma Medical Information.

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The Phase 1/2 study has enrolled a total of 27 patients. The Phase 2 portion of the study (n=21) was designed to assess the safety, tolerability, and anti-tumor activity of the full dose and schedule of PO tivozanib (1.5 mg/QD for 21 days followed by a 7-day rest period), as established in the Phase 1 portion of the study (n=6), in combination with IV nivolumab (240 mg every 2 weeks). The combination was generally well tolerated. Treatment-related Grade 3/4 adverse events occurred in 44% of patients, the most common of which was hypertension.

Preliminary efficacy was assessed in 14 patients treated with the full dose and schedule of PO tivozanib in combination with IV nivolumab and enrolled at least 4 months prior to the data cutoff date. Of these, seven had received at least one prior systemic therapy. An objective response rate was observed in 64% of patients (partial responses), and a disease control rate (partial response + stable disease) was observed in 100% of patients. At the time of data collection, 11 of 14 evaluable patients remained on study.

"These preliminary data continue to support the rationale for choosing a high-specificity VEGF inhibitor TKI, such as tivozanib, in building upon the benefit of immune checkpoint therapy in renal cancer," said Doctor Bernard Escudier, MD, ex-Chairman of the Genitourinary Oncology Committee, Gustave Roussy, and lead investigator of the study. "Combining VEGF TKIs and immune checkpoint inhibitors has been hampered by toxicity, potentially emerging with the use of other TKIs, while minimal off-target toxicities have been observed with tivozanib in this combination. These results open the possibility for triple-combination therapy using tivozanib, nivolumab and ipilimumab, an immune system activator targeting CTLA-4."

"We believe that VEGF TKI-immunotherapy combinations are the obvious next step in the evolution of treatment within mRCC, which underscores the need for a VEGF therapy with best-in-class safety," said Michael Needle, M.D., chief medical officer of AVEO. "The preliminary activity and favorable safety profile observed thus far in the TiNivo study are encouraging and support the further exploration of tivozanib combinations with immuno-oncology therapies. In addition to the TiNivo study, we continue to look forward to topline data in the second quarter of 2018 from our Phase 3 TIVO-3 study, which, together with the previously completed TIVO-1 trial of tivozanib in the first line treatment of mRCC, is designed to support a request for regulatory approval of tivozanib in North America as a first and third line treatment for mRCC."

Lee Morley, EUSA Pharma’s Chief Executive Officer said, "We are excited by the continued development potential for tivozanib and the data arising from initial studies in combination with checkpoint inhibitors. As an effective TKI with a favorable tolerability profile, we are already launching tivozanib across the EU in line with its recent approval as monotherapy in the first line setting, and on the basis of the TiNivo study, we look forward to the potential to develop new innovative treatment options for patients in the future."

About Tivozanib (FOTIVDA)

Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Hakko Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.1,2 Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models, enabling potentially enhanced activity when used in combination with immune modulating therapy. As part of a North American registration plan, Tivozanib is currently being studied in the Phase 3 TIVO-3 trial, a randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory advanced RCC. Tivozanib has been investigated in several tumors types, including renal cell, hepatocellular, colorectal and breast cancers.

lthough emerging immuno-oncology products have been able to elicit unprecedented responses in cancers that are easily accessible to immune cells (eg. leukemia), solid tumors may be resistant to such therapies. 7 Hills is developing cost effective, safe therapeutics to overcome such resistance. Our lead compounds have the potential to increase the antitumor activity of numerous emerging cell-based immunotherapies, and enable the use of recently approved drugs to treat solid tumors that are currently refractory to therapy.

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7HP compounds target validated cell adhesion pathways that are critical for T cell homing to specific tissues. They are the only known activators of both the VLA-4/VCAM-1 and LFA-1/ICAM-1 cell adhesion axes. Activation of these adhesion pathways could significantly increase the trafficking of endogenous effector lymphocytes (targets of checkpoint blockade therapeutics) or adoptively transferred effectors (like CAR-T cells) into solid tumors.

Pre-clinical studies have shown that 7HP lead compounds:

Increase the adhesion of activated T-cells to simulated tumor endothelium by 100 fold,
Increase the penetration of activated T-cells into simulated tumor stroma.

On February 9, 2018 Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing tumor-targeted and immuno-oncology therapies based on its pioneering research and development in cancer epigenetics, reported scientific and clinical presentations on its most advanced EZH2 and BET clinical development candidates at three upcoming conferences (Press release, Constellation Pharmaceuticals, FEB 9, 2018, View Source [SID1234523878]).

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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

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Keystone Symposia for Cancer Epigenetics: New Mechanisms, New Therapies

Title: EZH2 inhibitor treatment results in genome-wide EZH2 re-distribution to genes required for terminal differentiation of germinal center B cells
Session Name: Poster Session 1
Type: Poster Presentation
Presenter: CC Yuan
Date: February 11, 2018
Time: 7:30 to 10:00 p.m. MST (9:30 p.m. to midnight EST)
Location: Breckenridge Ballroom, Beaver Run Resort, Breckenridge, Colorado, USA

Epigenetics Conference: From Mechanisms to Disease

Title: Utilizing chemical biology to identify novel strategies targeting histone acetyl signaling in cancer
Session Name: Heterochromatin and Chemical Biology Approaches
Type: Oral Presentation
Presenter: Rob Sims
Date: February 17, 2018
Time: 11:15 to 11:45 a.m. EST
Location: Fiesta Americana Condesa Hotel, Cancun, Mexico

2018 International Targeted Anticancer Therapies (TAT) Congress/ESMO

Title: A Phase I Study of CPI-0610, a Bromodomain and Extra Terminal Protein (BET) Inhibitor in Patients with Relapsed or Refractory Lymphoma
Presentation Number: 41O
Session Name: Proffered Paper Session 2
Type: Oral Presentation
First Author: Kristie A. Blum
Presenter: Adrian Senderowicz
Date: March 6, 2018
Time: 11:00 to 11:12 a.m. CET (5:00 to 5:12 a.m. EST)
Location: Room Scene AB, Paris Marriott Rive Gauche, Paris, France

Title: A Phase 1 Study of CPI-1205, a Small Molecule Inhibitor of EZH2, Preliminary Safety in Patients with B-Cell Lymphomas
Presentation Number: 42O
Session Name: Proffered Paper Session 2
Type: Oral Presentation
First Author: Wael Harb
Presenter: Claudia Lebedinsky
Date: March 6, 2018
Time: 11:15 to 11:27 a.m. CET (5:15 to 5:27 a.m. EST)
Location: Room Scene AB, Paris Marriott Rive Gauche, Paris, France

About CPI-1205
CPI-1205 is an experimental small molecule therapy that is designed to inhibit the enzymatic activity of Enhancer of Zeste Homolog 2 (EZH2). The function of EZH2 is to selectively suppress gene expression of several tumor suppressor pathways and pathways that contribute to drug resistance.

About CPI-0610
CPI-0610 is an experimental small-molecule therapy designed to inhibit the expression of several genes involved in cancer and fibrosis, including MYC, BCL2, NF-κB and TGF-β-induced collagen by binding to a family of proteins known as bromodomain and extra-terminal (BET).

On February 9, 2018 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported recent highlights and operating results for the quarter and year ended December 31, 2017 (Press release, ImmunoGen, FEB 9, 2018, View Source [SID1234523879]).

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"We made significant progress with the business in 2017, with four consecutive quarters of strong execution across the Company. Operationally, we advanced our monotherapy registration study and published compelling combination data with mirvetuximab, expanded our clinical pipeline, and established a high-value partnership with Jazz Pharmaceuticals supporting our earlier-stage programs. Financially, we added over $235 million in cash and eliminated roughly $100 million in debt on the balance sheet through business development and financing transactions," said Mark Enyedy, ImmunoGen’s president and chief executive officer. "With the momentum we generated in the last twelve months, we enter 2018 from a position of strength with a number of important catalysts expected during the year. We anticipate completing patient enrollment in our FORWARD I Phase 3 registration trial by mid-year, multiple data readouts from our FORWARD II trial assessing combinations with mirvetuximab beginning next month at the Society of Gynecologic Oncology annual meeting, and clinical data from our Phase 1 trials of both IMGN779 and IMGN632 later in the year. With these anticipated events, we look forward to another productive year in 2018 as we advance our pipeline to bring new therapies to patients and create value for our shareholders."

Recent Pipeline Highlights

· Activated more than 100 sites in North America and Europe in the Company’s ongoing Phase 3 FORWARD I trial of mirvetuximab soravtansine as single-agent therapy for platinum-resistant ovarian cancer enabling rapid patient enrollment;

· Advanced the Company’s Phase 1b/2 FORWARD II trial in North America and Europe evaluating mirvetuximab soravtansine combination regimens in separate expansion cohorts with Keytruda (pembrolizumab) and Avastin (bevacizumab) for platinum-resistant disease, and initiated patient dosing in a new cohort to evaluate the triplet combination of mirvetuximab plus carboplatin and Avastin in patients with platinum-sensitive disease;

· Reported updated safety data and preliminary anti-leukemia activity from the dose-escalation phase of the Phase 1 clinical trial of IMGN779 in patients with acute myeloid leukemia (AML) at the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting;

· Began dosing patients in the Company’s Phase 1 clinical trial of IMGN632, a CD123-targeting ADC integrating a potent DNA-alkylating payload intended to treat a range of hematological malignancies, including AML and blastic plasmacytoid dendritic cell neoplasm (BPDCN); and

· Received notice that partner Takeda has filed an IND for TAK-164, an ADC directed to GCC-positive tumors using ImmunoGen’s IGN platform.

Facilities Update

· Following an in-depth review of the Company’s manufacturing strategy, ImmunoGen will move to an operating model that will rely on external manufacturing and quality testing for drug substance and drug product for its development programs. The implementation of this new operating model will lead to the ramp-down of manufacturing and quality activities at the Company’s Norwood, Massachusetts facility by the end of 2018, with a full exit of the site by early 2019. Decommissioning the Norwood facility will result in anticipated cost savings of over $20 million during the next five years.

· The Norwood facility has been a long-standing staple of ImmunoGen’s business, delivering high-quality products to patients and partners without interruption for more than 25 years. The Company is grateful for the contributions that its Norwood-based employees have made and will support these employees through the transition.

Anticipated 2018 Events

· Conduct interim analysis from FORWARD I, for futility only, in 1Q 2018;

· Report updated dose-escalation findings from the FORWARD II mirvetuximab plus Keytruda combination cohort at the Society of Gynecologic Oncology annual meeting (March 2018);

· Present highlights from ImmunoGen’s technology and innovation in ADCs at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting (April 2018);

· Anticipate partner Takeda to begin clinical development of TAK-164 in the first half of 2018;

· Report updated data from the FORWARD II mirvetuximab plus Avastin combination expansion cohort in over 50 patients in the first half of 2018;

· Complete patient enrollment in FORWARD I by mid-year;

· Report findings from the FORWARD II mirvetuximab plus Keytruda combination expansion cohort in over 30 patients the second half of the year;

· Report additional data from IMGN779 Phase 1 study in 4Q 2018;

· Report initial data from IMGN632 Phase 1 study in 4Q 2018; and

· Advance our ADAM9 program into IND-enabling activities before year-end.

Financial Results

As previously disclosed, effective January 1, 2017, ImmunoGen transitioned to a fiscal year ending December 31. The years ended December 31, 2017 and 2016 reflect the twelve-month results of the respective calendar years.

Revenues for the year ended December 31, 2017 were $115.4 million, compared to $48.6 million for the year ended December 31, 2016. License and milestone fees of $79.5 million for 2017 included a $30 million paid-up license fee related to an amendment to the Company’s collaboration and license agreement with Sanofi, $29.5 million related to the sale and transfer of the Company’s IMGN529 asset to Debiopharm, $7 million in partner milestone payments and $12.7 million in amortization of a non-cash fee related to the Company’s license agreement with CytomX, compared to $15 million in partner milestone payments received in 2016. Revenues for 2017 included $28.1 million in non-cash royalty revenues, compared with $26.2 million in non-cash royalty revenues for 2016. Revenues for 2017 also included $3.5 million of research and development (R&D) support fees and $4.4 million of clinical materials revenue, compared with $5.2 million and $1.9 million, respectively, for 2016.

Operating expenses, including R&D and G&A expenses, for 2017 were $174.4 million, compared to $184.3 million for 2016. R&D expenses for 2017 decreased to $139.7 million, compared to $141.3 million for 2016, primarily due to a workforce reduction resulting from the strategic review in September 2016 and lower third-party service fees, partially offset by increased clinical trial and drug supply costs driven largely by the advancement of the FORWARD I Phase 3 clinical trial. General and administrative expenses decreased in 2017 to $33.9 million, compared to $38.5 million in 2016, primarily due to lower personnel expenses. Operating expenses for 2016 also included a $4.4 million restructuring charge related to the workforce reduction and a loss on leased office space, compared to a $0.8 million charge in 2017 related to additional loss recorded on leased office space.

In September and November 2017, a total of $97.9 million of convertible debt outstanding was converted into 26.2 million shares of the Company’s common stock, resulting in a $22.9 million non-cash debt conversion charge recorded in 2017. With this conversion, the Company’s outstanding debt is reduced to $2.1 million. In October 2017, pursuant to a public offering, the Company sold an aggregate of 16.7 million shares of its common stock, with net proceeds to the Company of $101.7 million, after deducting underwriting discounts and offering expenses.

ImmunoGen reported a net loss of $96.0 million, or $0.98 per basic and diluted share, for 2017, which included a loss of $0.23 per basic and diluted share relating to the non-cash debt conversion charge, compared to a net loss of $156.7 million, or $1.80 per basic and diluted share, for 2016.

ImmunoGen had $267.1 million in cash and cash equivalents as of December 31, 2017, compared with $160.0 million as of December 31, 2016, and had $2.1 million and $100.0 million of convertible debt outstanding as of December 31, 2017 and December 31, 2016, respectively. Cash provided by operations was $7.6 million for 2017, compared with cash used in operations of $(142.6) million for 2016. The current year benefited from $59.5 million of fees received from Sanofi and Debiopharm, which were included in revenue for 2017, and a $75 million upfront

payment received from Jazz, which is included in deferred revenue as of December 31, 2017. Capital expenditures were $1.1 million and $6.7 million for 2017 and 2016, respectively.

Financial Guidance

For 2018, ImmunoGen expects:

· revenues between $60 million and $65 million;

· operating expenses between $185 million and $190 million; and

· cash and cash equivalents at December 31, 2018 between $115 million and $120 million.

ImmunoGen expects that its current cash combined with the expected cash revenues from partners and collaborators will enable the Company to fund its operations into the fourth quarter of 2019.

Conference Call Information

ImmunoGen will hold a conference call today at 8:00 am ET to discuss these results. To access the live call by phone, dial 719-325-4917; the conference ID is 5734226. The call may also be accessed through the Investors section of the Company’s website, www.immunogen.com. Following the webcast, a replay of the call will be available at the same location through February 23, 2018.

On February 9, 2018 Pieris Pharmaceuticals, Inc. (NASDAQ: PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform for cancer, respiratory and other diseases, and Seattle Genetics, Inc. (NASDAQ: SGEN), a global biotechnology company developing innovative, targeted therapies for cancer, reported they have entered into a collaboration and license agreement with the goal of developing multiple targeted bispecific immuno-oncology treatments for solid tumors and blood cancers (Press release, Seattle Genetics, FEB 9, 2018, View Source;p=RssLanding&cat=news&id=2331570 [SID1234523875]).

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The collaboration leverages the expertise and core technologies of both companies to develop novel Antibody-Anticalin fusion proteins. Pieris’ proprietary suite of agonistic costimulatory Anticalin proteins, when fused to a tumor-targeting antibody, can activate the immune system preferentially in the tumor microenvironment. Seattle Genetics, through its industry-leading work in the field of antibody-drug conjugates (ADCs), has a substantial portfolio of cancer targets and tumor-specific monoclonal antibodies from which programs will be selected for the collaboration. The bispecific drug candidates in this alliance will be designed to enable the patient’s immune cells to specifically attack tumors.

"As the industry leader in ADCs, we bring deep expertise in targeted cancer therapy development to this collaboration with Pieris," said Dennis Benjamin, Ph.D., Senior Vice President of Research at Seattle Genetics. "Pieris’ Anticalin technology and Antibody-Anticalin bispecific approach are intended to overcome the limitations of currently available immuno-oncology products. This partnership leverages our cancer targets and tumor-specific antibodies to explore multiple novel bispecific combinations, with the goal of developing targeted therapies that improve outcomes for people with cancer."

Under the terms of the agreement, Seattle Genetics will pay Pieris a $30 million upfront fee, tiered royalties on net sales up to low double-digits, and up to $1.2 billion in total success-based payments across three product candidates. The companies will pursue multiple Antibody-Anticalin fusion proteins during the research phase, and Seattle Genetics has the option to select up to three therapeutic programs for further development. Prior to the initiation of a pivotal trial, Pieris may opt into global co-development and US commercialization of the second program and share in global costs and profits on a 50/50 basis. Seattle Genetics will solely develop, fund and commercialize the other two programs.

"Pieris was the first company to bring a tumor-targeted costimulatory bispecific to patients with PRS-343, and we are looking forward to broadening our bispecific pipeline through this alliance. Seattle Genetics is a compelling partner for Pieris with a long-standing commitment to oncology," said Stephen S. Yoder, President and CEO of Pieris. "The collaboration combines the excellent protein engineering and translational capabilities of both companies, utilizing Seattle Genetics’ tumor-targeted monoclonal antibodies and Pieris’ Anticalin proteins to create novel bispecifics. This is our third significant alliance since January 2017 and is in alignment with our goal to create a respiratory- and oncology-focused commercial company."

About Anticalin Therapeutics:

Anticalin proteins are derived from lipocalins, small human proteins that naturally bind, store and transport a wide spectrum of molecules. Anticalin proteins feature the typical four-loop variable region and a rigidly conserved beta-barrel backbone of lipocalins, which, together, form a shapeable cup-like binding pocket. Proprietary to Pieris, Anticalin proteins are a novel class of protein therapeutics validated in the clinic and by partnerships with leading pharmaceutical companies. Anticalin is a registered trademark of Pieris.