On December 11, 2017 MacroGenics, Inc. (NASDAQ:MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as autoimmune disorders and infectious diseases, reported the presentation of clinical data from its ongoing Phase 1 study of flotetuzumab in an oral session at the 59th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Atlanta, Georgia (Press release, MacroGenics, DEC 11, 2017, View Source [SID1234522556]). John E. Godwin, M.D., Program Leader, Hematologic Malignancies at Earle A. Chiles Research Institute at Providence Cancer Center in Portland, Oregon presented "Preliminary Results of a Phase 1 Study of Flotetuzumab, a CD123 x CD3 Bispecific DART Protein, in Patients with Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome."

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The ongoing Phase 1, first-in-human study of flotetuzumab was designed to determine safety, tolerability, maximum tolerated dose and initial anti-leukemic activity in patients with relapsed or refractory acute myeloid leukemia (AML) or intermediate-2/high risk myelodysplastic syndrome (MDS). To date, a total of 57 patients have been enrolled, including 11 AML patients in the dose expansion cohort.

Consistent with the dose escalation data that was previously presented at ESMO (Free ESMO Whitepaper) Congress 2017 in September, flotetuzumab has continued to demonstrate acceptable tolerability in patients treated to date in the dose expansion cohort. Infusion-related reaction and cytokine release syndrome (CRS) were the most common adverse events observed, with Grade 3 CRS occurring in 9 of 57 patients (15.8%). Implementation of a two-step, lead-in dose as well as early intervention with anti-cytokine therapy has helped to limit the severity and incidence of CRS.

As of the data cut-off date, of the eight evaluable patients in the dose expansion cohort who received a lead-in dose followed by 500 ng/kg/day of flotetuzumab via continuous IV infusion, six patients (75%) have evidence of anti-leukemic activity, with three of these patients experiencing an objective response. This included two patients who experienced CR/CRi and one patient who achieved MLF (morphologic leukemia-free state).

The duration of response for the eight patients who have achieved a MLF, CRi or CR in the dose escalation and dose expansion cohorts ranged from 1.0 to 5.8 months, with five of these responses still ongoing as of the November 30, 2017 data cut-off.

Further, in a translational data poster presentation, MacroGenics also described studies that support a rationale for using checkpoint blockade as an approach to potentially enhance the anti-leukemic activity of flotetuzumab. Among these findings, modulation of the PD-1/PD-L1 pathway was observed in patients treated with flotetuzumab, and the combination of flotetuzumab and PD-1/PD-L1 inhibitors was shown to synergistically enhance T-cell mediated cytotoxicity against AML cell lines in vitro.

"We continue to be encouraged by the tolerability and anti-leukemic activity of flotetuzumab as well as by the early data regarding the durability of responses observed in patients from our ongoing Phase 1 study of flotetuzumab," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "In addition, given the data-supported rationale for combining flotetuzumab with anti-PD-1, we intend to initiate a combination study with the anti-PD-1 mAb, MGA012, in the coming months, while we continue to enroll the AML and MDS dose expansion cohorts. We look forward to sharing additional flotetuzumab clinical data in 2018."

The presentation at the 59th Annual ASH (Free ASH Whitepaper) meeting is available for download from the Events & Presentations page on MacroGenics’ website at View Source

About Flotetuzumab

Flotetuzumab (also known as MGD006 and S80880) is a clinical-stage molecule that recognizes both CD123 and CD3. CD123, the Interleukin-3 receptor alpha chain, has been reported to be over-expressed on cancer cells in a wide range of hematological malignancies, including AML and MDS. The primary mechanism of action of flotetuzumab is believed to be its ability to redirect T lymphocytes to kill CD123-expressing cells. To achieve this, the DART molecule combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123 on the target cancer cells.

Flotetuzumab is currently being evaluated at 13 clinical sites in the U.S. and Europe in a Phase 1 study designed to assess the safety, tolerability, maximum tolerated dose and initial anti-leukemic activity of the molecule in patients with relapsed/refractory AML or intermediate-2/high risk MDS. MacroGenics retains full development and commercialization rights to flotetuzumab in the U.S., Canada, Mexico, Japan, South Korea and India. Servier participates in the development of flotetuzumab and has exclusive rights to this molecule in all other countries. The U.S. Food and Drug Administration has granted orphan drug designation to flotetuzumab for the treatment of AML.

On December 11, 2017 IMMUNOPRECISE ANTIBODIES LTD. (the "Company") (TSX VENTURE: IPA)(OTC PINK: IPATF) reported that it has signed a binding letter of intent with ModiQuest Research BV ("ModiQuest") whereby the Company has agreed to acquire all of the issued and outstanding shares of ModiQuest (the "Transaction") (Press release, ModiQuest Therapeutics, DEC 11, 2017, View Source [SID1234522558]).

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The Transaction continues to realize on the Board’s commitment to grow globally through strategic acquisitions. It allows IPA to become a single source provider of services across the full antibody discovery value chain (antigen design, hit generation, lead selection, lead optimization and lead characterization) and to offer the full spectrum of antibody production methodologies (library based technologies, hybridoma methods, transgenic animal based platforms and single B cell based technology). Furthermore, the acquisition enhances the Company’s capacity for generating human antibodies.

"In acquiring ModiQuest Research B.V., IPA becomes a leading integrated antibody solutions company with global reach," said Dr. James Kuo, Chairman, Interim President of the Company.

ModiQuest

ModiQuest is a privately held company based in Oss, The Netherlands that specializes in the generation of monoclonal antibodies against difficult target antigens. ModiQuest applies proprietary technologies to all aspects of the antibody discovery process in research and development, diagnostic and therapeutic applications. Using its proprietary ModiFuse (hybridoma electrofusion), ModiSelect (B-cell selection) and ModiPhage (phage display) technologies, ModiQuest can generate very large panels of monoclonal antibodies from various backgrounds including mouse, rat, rabbit, chicken, llama and human, as well as transgenic animals harboring the human antibody gene repertoire. ModiQuest serves clients in Europe, the US, Asia and Russia. During its year-ended 2016, ModiQuest had revenues of €2,009,374 (CAD $3,037,249) and earnings of €671,799 (CAD $1,015,451).

The Transaction is accretive in both revenue and earnings and brings additional scientific and management capacity.

Terms of Transaction with ModiQuest

Under the binding letter of intent, the Company and ModiQuest have agreed to negotiate a definitive agreement (the "Definitive Agreement") whereby the Company will acquire all of the issued and outstanding shares of ModiQuest for €7,000,000 (CAD$10,570,000) (the "Purchase Price"), of which (A) €2,500,000 (CAD$3,775,000) will be paid in cash on closing, (B) €2,500,000 (CAD$3,775,000) will be satisfied by the issuance of approximately 6,622,807 common shares of the Company on closing, and (C) €2,000,000 (CAD$3,020,000) in deferred payments over a three year period (the "Deferred Payments"). The Deferred Payments will be made in three equal installments of cash and equity totaling €666,666 (CAD$1,006,665) on each anniversary date following closing of the transaction. The Deferred Payments will be prorated if the EBITDA of ModiQuest fails to equal the average EBITDA from the previous two years. ImmunoPrecise expects to finance the cash portion of the purchase price using a convertible debt instrument.

The letter of intent also requires that Jos Raats, a principal of ModiQuest, to enter into a three year management contract, which will include non-solicitation and non-competition clauses, and Mr. Raats will provide a minimum of 60% of full time employment to ModiQuest under the management contract. The Company has also agreed to appoint one of the principal shareholders of ModiQuest to its board of directors.

The parties will be entitled to carry out due diligence of each other until February 15, 2018. Upon the parties completing due diligence to their reasonable satisfaction, the parties will enter into the Definitive Agreement setting forth the terms and conditions of the Transaction by February 28, 2018. Completion of any transaction with ModiQuest is subject to a number of conditions, including but not limited to, completion of due diligence, negotiation of definitive agreements in respect of such a transaction, the availability of financing on terms acceptable to the Company, and receipt of any required regulatory and shareholder approvals. A transaction cannot be completed until these conditions are satisfied, and there can be no assurance that a transaction will be completed at all.

On December 11, 2017 Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a company committed to improving patient lives by manufacturing and delivering high quality biologics, reported financial results for the second quarter of fiscal year (FY) 2018 ended October 31, 2017, and provided an update on its contract manufacturing operations, and other corporate highlights (Press release, Peregrine Pharmaceuticals, DEC 11, 2017, View Source [SID1234522560]).

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Highlights Since July 31, 2017

"Today, we are pleased to report that the company has made great progress in its transition from an R&D focused business to a dedicated contract development and manufacturing organization (CDMO)," stated Roger J. Lias, Ph.D., president of Avid Bioservices. "In late November, the company came to an agreement with an investor group, appointing a highly qualified new board of directors consisting of three new independent members from this investor group and one mutually designated independent member in addition to myself and the two independent members previously appointed. We have now added six highly qualified and independent board members since October. In addition, we are focused on hiring experienced and successful CDMO professionals who are dedicated to revenue growth through the expansion and diversification of Avid’s client base, as evidenced by the recently announced hiring of Tracy Kinjerski as vice president of business operations. We are actively planning to expand Avid’s service offerings and enhance our manufacturing infrastructure to ensure that we are offering the highest quality services, and state-of-the-art facilities to our customers. We are also taking steps to officially change the name of the entire organization to Avid Bioservices, Inc. to formalize this transition. Lastly, we are in continued discussions with third parties regarding the divestiture of the company’s remaining R&D assets and we will keep you apprised on our progress as we advance the process."
Recent Developments at Avid Bioservices

Established a dedicated CDMO management infrastructure with the hiring of Roger J. Lias, Ph.D., as the President of Avid Bioservices and director.

• Dr. Lias brings more than 20 years of experience in the industry having held senior management positions at several leading CDMOs including Cytovance Biologics, KBI BioPharma, Diosynth RTP (formerly Covance Biotechnology Services) and Lonza Biologics.

Strengthened Avid’s sales and business development function with the hiring of Tracy Kinjerski as vice president of business operations.
• Ms. Kinjerski brings more than 17 years of experience with a focus in contract development and manufacturing. She is charged with driving Avid’s growth through the strategic expansion and diversification of the company’s commercial and clinical client base.

Reconstituted the board of directors to include six independent directors, all with significant CDMO experience.
• In October 2017, Mark R. Bamforth was appointed as an independent member of the board of directors. Mr. Bamforth has 30 years of biologics leadership experience including founding two CDMOs, Brammer Bio, where he is currently the president and CEO, and Gallus BioPharmaceuticals, which was acquired by DPx Holdings B.V., the parent company of Patheon. Additionally, he served for more than 20 years in key roles at Genzyme Corporation, including 10 years as a corporate officer responsible for running global manufacturing.

• In October 2017, Patrick Walsh was appointed as an independent member of the board of directors. Mr. Walsh has a record of leading successful, high-growth CDMOs and he has also led complex laboratory and pharmaceutical manufacturing operations including parenteral and active pharmaceutical ingredients (API) on a global scale.

• In November 2017, the company entered into a settlement agreement with its largest shareholder (Ronin/SWIM) regarding the composition of Peregrine’s board of directors. Under the terms of the Agreement, on November 27, 2017, directors Steven W. King, Carlton M. Johnson, Jr., Eric S. Swartz and David H. Pohl each tendered his resignation, effective immediately, from Peregrine’s board of directors, and from the board of directors of Avid Bioservices. The vacancies created by these resignations were immediately filled by three individuals who were nominated by Ronin/SWIM for election at Peregrine’s upcoming 2017 Annual Meeting of Stockholders (Richard B. Hancock, Gregory P. Sargen and Joel McComb), and one director (Joseph Carleone, Ph.D.) who is independent of Ronin/SWIM and new to Peregrine.

• Joseph Carleone, Ph.D. (independent appointee): Dr. Carleone is Chairman of the Board of AMPAC Fine Chemicals LLC, a leading manufacturer of pharmaceutical active ingredients. Prior to this position, Dr. Carleone was President, Chief Executive Officer and director of American Pacific Corporation, a leading custom manufacturer of fine and specialty chemicals and propulsion products.

• Richard B. Hancock (Ronin/SWIM appointee): Richard (Rick) B. Hancock has worked in the biologic CDMO industry for over 30 years in various operational and executive roles, serving most recently as President and CEO of Althea Technologies, Inc., a large molecule CDMO producing a wide range of biologics, vaccines and parenteral products.

• Joel McComb (Ronin/SWIM appointee): Joel McComb is the CEO, Chairman and Co-Founder of BioSpyder Technologies, Inc. Prior to BioSpyder, Mr. McComb served as Senior Vice President and General Manager of Illumina, Inc., President of GE Healthcare’s Life Sciences and Discovery Systems division, and President of GE Healthcare’s Interventional Medicine division.

• Gregory P. Sargen (Ronin/SWIM appointee): Gregory P. Sargen currently serves as Executive Vice President – Corporate Development and Strategy of Cambrex Corporation ("Cambrex"), a global manufacturer and provider of services to life sciences companies. Prior to his current role, Mr. Sargen served as Executive Vice President and Chief Financial Officer of Cambrex.

Expanded production capacity in the Myford facility to allow organic and significant growth using existing facilities.

• In recent months, the company expanded its capacity in its Myford facility by installing two new 2,000 liter single-use bioreactors.
Financial Highlights and Results
The company maintains its manufacturing revenue guidance for the full FY 2018 of $50 million – $55 million.

Contract manufacturing revenue from Avid’s clinical and commercial biomanufacturing services was $12.8 million for the second quarter of FY 2018 compared to $23.4 million for the second quarter of FY 2017.

Avid’s current manufacturing revenue backlog is $33.0 million, representing estimated future manufacturing revenue to be recognized under committed contracts. Most of the backlog is expected to be recognized during the remainder of FY 2018 and into FY 2019.

Total operating expenses for the second quarter of FY 2018 were $9.2 million, compared to $12.0 million for the second quarter of FY 2017. For the second quarter of FY 2018, total operating expenses included restructuring charges of $1.6 million associated with termination benefits including severance and other employee related costs related to a workforce reduction pursuant to a restructuring plan implemented in August 2017. The company is also actively evaluating its overall operating expenses and cost structure as a dedicated CDMO and plans to align its cost structure to match the future needs of the business.

Research and development expenses decreased to $3.7 million in the second quarter of FY 2018 compared to $7.0 million for the second quarter of FY 2017. Over the next 60 or fewer days, the Company will continue to rapidly wind down all research and development costs to zero and plans to support only those efforts needed to pursue the license or sale of its research and development assets.

Cost of contract manufacturing increased to $16.2 million in the second quarter of FY 2018 compared to $15.4 million for the second quarter of FY 2017.

For the second quarter of FY 2018, selling, general and administrative expenses decreased to $3.9 million compared to $5.0 million for FY 2017.

Peregrine’s consolidated net loss attributable to common stockholders was $14.1 million or $0.31 per share, for the second quarter of FY 2018, compared to a net loss attributable to common stockholders of $5.5 million, or $0.16 per share, for the same prior year quarter.

Peregrine reported $27.7 million in cash and cash equivalents as of October 31, 2017, compared to $46.8 million at fiscal year ended April 30, 2017. As further discussed in the Company’s Quarterly Report on Form 10-Q, the Company plans to raise additional capital within the next six months to support its continued operations and other initiatives that will enhance its CDMO operations.
More detailed financial information and analysis may be found in Peregrine’s Quarterly Report on Form 10-Q, which will be filed with the Securities and Exchange Commission today.

Conference Call
Peregrine will host a conference call and webcast this afternoon, December 11, 2017, at 4:30 PM EST (1:30 PM PST).
To listen to the conference call, please dial (877) 312-5443 or (253) 237-1126 and request the Peregrine Pharmaceuticals conference call. To listen to the live webcast, or access the archived webcast, please visit: View Source

On December 11, 2017 Spark Therapeutics (NASDAQ:ONCE), a fully integrated gene therapy company dedicated to challenging the inevitability of genetic disease, and Pfizer Inc. (NYSE:PFE), reported that, with a cumulative follow-up of more than 13 patient years of observation, all 11 participants in the ongoing Phase 1/2 clinical trial of investigational SPK-9001 for the treatment of patients with hemophilia B had discontinued routine infusions of factor IX concentrates and shown sustained steady-state factor IX activity levels with no serious adverse events, thrombotic events or factor IX inhibitors observed (Press release, Pfizer, DEC 11, 2017, View Source [SID1234522561]). Based on individual participant history for the year prior to the study, the overall annualized bleeding rate (ABR) was reduced by 97 percent (calculated based on data after week four; 95 percent based on data after infusion) to a mean of 0.3 (0.5) annual bleeds, compared to a mean of 10.5 bleeds annually before SPK-9001 administration. Overall annualized infusion rate (AIR) was reduced 99 percent (calculated based on data after week four; 97 percent based on data after infusion) to a mean of 0.8 (1.7) annual infusions, compared to a mean of 62.5 infusions per year before SPK-9001 administration. Data on all 11 participants were presented today by Lindsey A. George, M.D., attending physician in the Division of Hematology at Children’s Hospital of Philadelphia and principal investigator of the trial, at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Atlanta.

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"We believe these longer-term data are meeting critical goals of our hemophilia programs," said Katherine A. High, M.D., president and head of research and development at Spark Therapeutics. "Now, with four participants followed for more than 18 months, we continue to see consistent levels of factor IX activity, no serious adverse events, as well as a sustained reduction in both the symptoms of hemophilia and the prophylactic and disease management protocols that were used prior to infusion with SPK-9001."

As of the Nov. 29, 2017 data cutoff, the mean steady-state factor IX activity level at 12 weeks post-administration for the 11 participants was 36 percent of normal (range as of the data cutoff: 15 to 78 percent). As of the data cutoff, the last participant to be infused, who received SPK-9001 manufactured using an enhanced process, was out eight months following SPK-9001 infusion, with a mean factor IX activity level of 60 percent. Spark Therapeutics will enroll up to four additional participants in the current Phase 1/2 clinical trial who will receive SPK-9001 manufactured using an enhanced process to test its comparability to the SPK-9001 received by the first 10 participants enrolled in the ongoing trial.

In this open-label, non-randomized and multicenter Phase 1/2 clinical trial, there were no serious adverse events during or following infusion with SPK-9001, and no participants experienced thrombotic events or developed factor IX inhibitors. Two participants developed an asymptomatic and transient increase in liver enzymes that resolved with a tapering dose of oral corticosteroids. One participant with severe joint disease administered factor for suspected joint bleeding, while a second participant recorded one spontaneous bleed.

About Hemophilia B
Hemophilia, a rare genetic bleeding disorder that causes the blood to take a long time to clot because of a deficiency in one of several blood clotting factors, is almost exclusively found in males. People with hemophilia are at risk for excessive and recurrent bleeding from modest injuries, which have the potential to be life threatening. People with severe hemophilia often bleed spontaneously into their muscles or joints, or rarely into other critical closed spaces such as the intracranial space, where bleeding can be fatal. The incidence of hemophilia B is one in 25,000 male births. People with hemophilia B have a deficiency in clotting factor IX, a specific protein in the blood. Hemophilia B also is called congenital factor IX deficiency or Christmas disease. The current standard of care requires recurrent intravenous infusions of either plasma-derived or recombinant factor IX to control and prevent bleeding episodes. There exists a significant need for novel therapeutics to treat people living with hemophilia.

About the SPK-FIX Program and SPK-9001
SPK-9001 is a novel investigational vector that contains a bio-engineered adeno-associated virus (AAV) capsid and a codon-optimized, high-activity human factor IX gene enabling endogenous production of factor IX.

Spark Therapeutics and Pfizer entered into a collaboration in December 2014 for the SPK-FIX program, including SPK-9001, under which Spark Therapeutics is responsible for conducting all Phase 1/2 studies for any product candidates, while Pfizer will assume responsibility for pivotal studies, any regulatory activities and potential global commercialization of any products that may result from the collaboration.

On December 11, 2017 Seattle Genetics, Inc. (NASDAQ:SGEN) and Bristol-Myers Squibb Company (NYSE:BMY) reported highlighted updated interim results from an ongoing phase 1/2 clinical trial evaluating the combination of ADCETRIS (brentuximab vedotin) and Opdivo (nivolumab) in relapsed or refractory classical Hodgkin lymphoma (HL) at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place in Atlanta, Georgia, December 9-12, 2017 (Press release, Seattle Genetics, DEC 11, 2017, View Source;p=RssLanding&cat=news&id=2322109 [SID1234522562]). The data were also simultaneously published online in the journal Blood. The data reported from 62 patients, including 60 evaluable for response, were featured in an oral presentation and selected to be included in the 2018 Highlights of ASH (Free ASH Whitepaper) post-meeting program. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL that plays a role in tumor growth and survival. Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to harness the body’s own immune system to help restore anti-tumor immune response. ADCETRIS and Opdivo are not approved in combination for the treatment of relapsed or refractory HL or for other indications.

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"The phase 1/2 study combining the antibody-drug conjugate ADCETRIS with the PD-1 immune checkpoint inhibitor Opdivo is a promising investigational approach as it combines a CD30-targeted therapy with a therapy designed to activate the immune system. The antitumor activity of the drugs may be enhanced when administered in combination," said Alex Herrera, M.D., lead trial investigator and assistant professor at the City of Hope Medical Center, Duarte, California. "The interim results evaluating the combination regimen in relapsed or refractory HL patients continue to look compelling, demonstrating both promising activity in addition to a manageable overall safety profile. These data support further exploration of this novel, chemotherapy-free investigational regimen in HL patients."

"We are evaluating ADCETRIS broadly as the foundation of care for CD30-expressing lymphomas, including combination strategies that have the potential to improve efficacy. At this year’s ASH (Free ASH Whitepaper) Annual Meeting, we are presenting significant clinical updates that support this goal, including results from the phase 3 ECHELON-1 clinical trial evaluating ADCETRIS in combination with chemotherapy in frontline HL as well as interim results from this phase 1/2 study evaluating ADCETRIS in combination with Opdivo in relapsed HL," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "Interim results from the trial evaluating ADCETRIS in combination with Opdivo as pre-transplant salvage therapy for classical HL patients continue to look promising, demonstrating an 83 percent objective response rate, with a 62 percent complete response rate and an acceptable safety profile. We look forward to further evaluation of this innovative combination regimen in other disease settings, including the ongoing pivotal phase 3 CHECKMATE 812 study in patients with relapsed HL, in partnership with Bristol-Myers Squibb."

"Our ongoing collaboration to evaluate Opdivo in combination with Seattle Genetics’ ADCETRIS reinforces Bristol-Myers Squibb’s commitment to addressing cancer from all angles for patients with high unmet needs," said Fouad Namouni, M.D., head of Oncology Development, Bristol-Myers Squibb. "We look forward to further evaluation of the ADCETRIS and Opdivo combination in Hodgkin lymphoma and other hematologic malignancies in several ongoing trials."

Interim Results from a Phase 1/2 Study of Brentuximab Vedotin in Combination with Nivolumab in Patients with Relapsed or Refractory Hodgkin Lymphoma (Abstract #649, oral presentation at 10:30 a.m. ET)

Data were reported from 62 patients with relapsed or refractory HL who received the combination regimen of ADCETRIS plus Opdivo after failure of frontline therapy. Patients were treated once every three weeks, with up to four cycles of combination therapy in the outpatient setting. After completion of the fourth cycle of treatment, patients were eligible to undergo an autologous stem cell transplant (ASCT). The median age of patients was 36 years. The majority of patients (95 percent) were refractory or had relapsed after receiving the standard of care frontline treatment ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine) or some variation of the standard of care (ABVE-PC, R-ABVD).

Key findings presented include:

Of 60 response-evaluable patients, 50 patients (83 percent) had an objective response, including 37 patients (62 percent) with a complete response and 13 patients (22 percent) with a partial response. Five patients (eight percent) had stable disease and five patients (eight percent) had progressive disease. Median follow-up time was eight months and median duration of response was not yet reached. The estimated six-month progression-free survival rate was 89 percent.
Of the 62 patients enrolled, 58 patients completed all four cycles of study treatment and four patients discontinued prior to the end of treatment. At the time of data analysis, 54 patients received an ASCT. Preliminary analysis shows no impact of combination treatment with ADCETRIS and Opdivo on stem cell mobilization or engraftment.
The most common adverse events (AEs) of any grade occurring prior to ASCT or subsequent salvage therapy in at least 20 percent of patients were nausea, fatigue, infusion-related reaction (IRR), pruritus, diarrhea, headache, cough, vomiting, dyspnea, nasal congestion, pyrexia and rash. Grade 3 or 4 adverse events occurred in 19 patients (31 percent), with 17 patients (28 percent) having Grade 3 AEs (fatigue, IRR, pruritus and diarrhea) and two patients (three percent) having Grade 4 AEs (thrombocytopenia and increased lipase).
Infusion-related reactions (IRRs) were observed in 44 percent of patients, of which the majority (41 percent) were Grade 1 or 2. No patients discontinued treatment due to an IRR.
Potential immune-related adverse events, excluding IRRs, occurred in 50 patients (82 percent), and five patients required treatment with systemic steroids, including patients with Grade 3 diarrhea and Grade 2 colitis, Grade 3 aspartate aminotransferase elevation, Grade 4 colitis and pneumonitis (after receiving additional salvage therapy), Grade 2 pneumonitis, and Grade 4 pneumonitis (after BEAM, as part of the conditioning regimen). No patients discontinued treatment due to an immune-related adverse event.
ADCETRIS and Opdivo are being evaluated as combination therapy in multiple ongoing clinical trials. In addition to the study presented at ASH (Free ASH Whitepaper), a trial titled "A Safety and Effectiveness Study of Nivolumab in Combination With Brentuximab Vedotin to Treat Non-Hodgkin Lymphomas" is ongoing and enrolling patients with relapsed or refractory disease, including diffuse large B-cell lymphoma (DLBCL), and other rare subtypes of B-cell lymphoma, including mediastinal B-cell lymphoma and mediastinal gray zone lymphoma. The companies have also extended the clinical evaluation of ADCETRIS and Opdivo into a clinical trial evaluating the combination as frontline treatment for older HL patients. Lastly, the companies initiated a pivotal phase 3 clinical trial called CHECKMATE 812 trial evaluating ADCETRIS alone versus ADCETRIS in combination with Opdivo in relapsed/refractory HL patients.

About Classical Hodgkin Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system and is the most common type of blood cancer. There are two major categories of lymphoma: HL, also known as Hodgkin disease, and non-Hodgkin lymphoma. HL is a cancer that starts in white blood cells called lymphocytes, which are part of the body’s immune system. The disease is most often diagnosed in early adulthood (ages 20-40) and late adulthood (older than 55 years of age). Classical Hodgkin lymphoma is the most common type of HL, accounting for 95% of cases. Classical HL is distinguished from other lymphomas by the characteristic presence of CD30-positive Reed-Sternberg cells.

According to the American Cancer Society, approximately 8,260 cases of Hodgkin lymphoma will be diagnosed in the United States during 2017 and more than 1,000 will die from the disease. According to the Lymphoma Coalition, over 62,000 people worldwide are diagnosed with Hodgkin lymphoma each year and approximately 25,000 people die each year from this cancer.

About ADCETRIS

ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30 and is being evaluated broadly in more than 70 clinical trials, including three phase 3 studies: the completed ECHELON-1 trial in frontline classical Hodgkin lymphoma that supported the recent FDA Breakthrough Therapy Designation and submission of the supplemental Biologics License Application (BLA) for use in this setting, the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, and the ongoing CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS injection for intravenous infusion has received FDA approval for four indications: (1) regular approval for adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy, (2) regular approval for the treatment of patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (3) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (4) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-ASCT consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. The European Commission extended the current conditional marketing authorization of ADCETRIS and approved ADCETRIS for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT.

ADCETRIS has received marketing authorization by regulatory authorities in 69 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo + Yervoy combination was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.