On March 30, 2017 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with a clinical stage pipeline of immune checkpoint antibodies and cancer vaccines, reported that it is reorganizing its business and operations to sharpen its focus on clinical development of its two checkpoint inhibitor antibodies and vaccine program (Filing, Agenus, MAR 30, 2017, View Source [SID1234518345]). Agenus plans to close its Basel site and consolidate key functions to its Cambridge, UK and Lexington, MA facilities, and phase out approximately 50 positions across the organization. Additionally, Robert Stein, M.D., Ph.D., President of R&D, will retire to become a senior R&D advisor exclusive to Agenus.

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Agenus’ goals for this realignment are to:

Accelerate development and commercialization of its product portfolio to drive shareholder value
Further extend the Company’s cash runway beyond the impact from the recently amended Incyte partnership, which strengthened the balance sheet by $80 million and reduced development expenses
Consolidate operations to improve R&D efficiencies
Ensure commercial readiness and manufacturing
Prioritized programs include combination therapies targeting CTLA-4 and PD-1. In addition, Agenus will continue to drive its innovative immuno-oncology portfolio towards clinical development with two preclinical antibodies targeting 4-1BB and TIGIT, as well as AutoSynVax, a clinical-stage neoantigen cancer vaccine. The Company is exploring combination studies with AutoSynVax and Agenus’ checkpoint antibodies. Substantial focus will also be placed on the Company’s manufacturing operations in Berkeley, CA to ensure GMP readiness. This is particularly pertinent as Agenus progresses its clinical registration trials with an intent to commercialize within the next four years.

As part of the restructuring, approximately 50 positions are planned to be phased out within the next six months. In addition, the Company will transition or consolidate certain key management positions, with the objective of streamlining leadership and reducing costs.

"These changes to our organizational structure make us a leaner and more focused organization, which is critically important for our next phase of advancement towards commercial readiness. We will also maintain a focused R&D effort to rapidly generate and develop best of breed novel immuno-oncology candidates. It is important to indicate that as an agile and efficient company we aim to rapidly deliver effective treatments at affordable prices," commented Dr. Armen.

Having built an extraordinary R&D capability for Agenus and spearheaded the advancement of five programs from discovery to clinical stage in the last three years, Dr. Robert Stein will be retiring from his current role as President of R&D and will become a senior R&D advisor to Agenus. The current R&D leadership, which has been assembled under his tutelage, will continue to have access to Dr. Stein for strategic R&D guidance.

"We are grateful to Dr. Stein for his outstanding leadership and contributions in defining and building our research engine," said Dr. Armen. "I look forward to continuing to work with him very closely in the future. I would also like to acknowledge the contributions of our other colleagues who will be departing the Agenus organization."

On March 30, 2017 Affimed N.V. (Nasdaq: AFMD), a clinical stage biopharmaceutical company focused on discovering and developing highly targeted cancer immunotherapies, reported financial results for the quarter and year ended December 31, 2016 (Filing, Q4/Annual, Affimed, 2016, MAR 30, 2017, View Source [SID1234518344]).

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"Throughout 2016, we expanded our leadership position in NK-cell engagement and made considerable progress both with our clinical and preclinical programs," said Dr. Adi Hoess, CEO of Affimed. "We have successfully executed on our strategy to broaden our efforts in combination therapies, advancing our clinical trial for AFM13 with Merck’s Keytruda as well as initiating our collaboration with MD Anderson to combine our NK-cell engagers with MD Anderson’s adoptive NK-cell transfer."

Corporate Updates

· In January 2017, Affimed and The University of Texas MD Anderson Cancer Center (MDACC) announced an exclusive strategic clinical development and commercialization collaboration to evaluate Affimed’s tetravalent bispecific immune cell engager technology in combination with MDACC’s natural killer (NK-) cell product. The collaboration comprises research, development, and eventually commercialization of novel oncology therapeutics resulting from this combination of products. MDACC will be responsible for conducting preclinical research activities and these are intended to be followed by a Phase 1 clinical trial. Affimed will fund research and development expenses for this collaboration and the agreement includes a provision for the potential expansion of the partnership. Affimed holds an option to exclusive worldwide rights to develop and commercialize any product developed under the collaboration. Leveraging MDACC’s expertise in NK-cells and translational medicine, and Affimed’s capabilities to develop tumor-targeting bispecific tetravalent immune cell engagers, the combination is initially planned to investigate Affimed’s AFM13, a CD30/CD16A-targeting tetravalent bispecific antibody, with MDACC’s proprietary NK-cell product in HL. Harnessing the advantages of both antibody-based and cell therapy approaches, this combination has the potential to better exploit the therapeutic activity of NK-cells in HL and beyond, for example in other medically underserved indications such as multiple myeloma or acute myeloid leukemia.

· In January and February 2017, Affimed completed an underwritten public offering on the Nasdaq Global Market, raising a total of approximately US $17.7 million (€16.5 million) in net proceeds. Proceeds from this transaction are expected to fund operations, including clinical development and early development activities, at least until the end of 2018.

· The Company entered into a loan agreement with Silicon Valley Bank in November 2016 for up to €10.0 million. The loan is available in two tranches, the first of which (€5.0 million) was drawn in December 2016. The Company may draw up to an additional €5.0 million on or before May 31, 2017, contingent on the Company’s satisfaction of certain conditions. The then-existing loan outstanding to Perceptive was repaid.

· The Company has recently entered into a termination agreement with its COO, Dr. Jörg Windisch, who will be leaving the Company at the end of June 2017. Dr. Windisch has accepted a position on the executive committee of a non-competing company focusing on the large-scale manufacturing of biologics and the development of biosimilars. He will continue to support Affimed as a consulting expert following his departure.

· Affimed’s subsidiary AbCheck announced achievement of the first clinical milestone in its antibody discovery collaboration with Eli Lilly and Company in January 2017. The milestone, the commencement of patient enrollment for a Phase 1 study of an antibody discovered under the collaboration agreement, triggered an undisclosed payment to AbCheck from Eli Lilly and represents an important validation of AbCheck’s technology suite and its capability to reliably deliver high-quality antibodies suitable for clinical development.

· Moving beyond its tetravalent, bispecific tandem diabodies (TandAbs), Affimed is broadening its immune cell engager capabilities. Building on the Company’s team’s unique antibody engineering expertise, Affimed is developing a suite of multivalent, multi-specific antibody formats for NK- and T-cell engagement. These novel antibody formats have the potential to tailor immune-engaging therapy to different indications and target populations.


Pipeline Updates

NK-cell engager programs
· In May 2016, Affimed initiated a Phase 1b combination study of AFM13 with Keytruda (pembrolizumab) in Hodgkin lymphoma (HL), No dose-limiting toxicities for the combination were observed in the first and second dose cohorts of the study. The overall safety profile determined for the combination was unchanged from that described for each drug alone in these cohorts. Data read-out is ongoing and the study has recently completed recruitment into the third dose cohort. The Company intends to provide an update on the study in the second half of 2017.

2

· For the Company’s investigator-sponsored Phase 2a monotherapy of AFM13 in HL, the study’s sponsor, the German Hodgkin Study Group (GHSG), and Affimed have revised the overall study design in order to adapt to the changing treatment landscape, namely the availability of anti PD-1 antibodies. The study will now include HL patients relapsed or refractory to treatment with both brentuximab vedotin and anti-PD-1, and different dosing protocols of AFM13 are being explored to allow for improved exposure in this more heavily pretreated patient population. Affimed continues to anticipate providing an update on the study in the second half of 2017, with the study expected to begin recruiting under the new design in the first half of 2017. In addition, Affimed also expects to report data collected from specific patient subsets enrolled under the original study protocol.

· Affimed has demonstrated in recent preclinical studies that AFM13 induced upregulation of specific interleukin receptors on NK-cells in a target-dependent manner and sensitized NK-cells to IL-2- or IL-15-mediated expansion. This provides a rationale for clinical combination of NK-cell engagers with cytokines aiming for deeper clinical responses. Affimed plans to provide an update on preclinical data supporting this approach at the upcoming AACR (Free AACR Whitepaper) Annual Meeting in early April 2017.

· Affimed continues to develop first-in-class NK-cell engagers to address the critical unmet need to effectively treat epidermal growth factor receptor (EGFR)-expressing solid tumors such as lung, head & neck and colon cancers. AFM24, an EGFR/CD16A-targeting tetravalent bispecific antibody, is designed to improve both efficacy and safety of current therapeutic monoclonal antibodies. AFM24 lead candidates are being developed to offer different PK/PD profiles relevant to certain diseases. Affimed plans to provide an update on its EGFR-targeting antibodies at the upcoming AACR (Free AACR Whitepaper) Annual Meeting in early April 2017.

· Affimed is developing AFM26 to treat multiple myeloma (MM), the second most common hematological cancer. AFM26 is a first-in-class tetravalent bispecific antibody targeting BCMA/CD16A. MM is characterized by high serum levels of monoclonal immunoglobulin (M-protein) and most patients eventually relapse with and/or become refractory to the currently available treatments. Importantly, AFM26’s NK-cell binding appears to be virtually unaffected by the presence high levels of IgG. Preclinical investigations are ongoing and Affimed plans to provide an update on AFM26 at the upcoming AACR (Free AACR Whitepaper) Annual Meeting in early April 2017.

T-cell engager programs
· In September 2016, the Company initiated a Phase 1 dose-escalation trial of its tetravalent bispecific CD19/CD3-targeting antibody AFM11 in patients with relapsed and refractory acute lymphocytic leukemia (ALL). The trial is ongoing and trial sites in the Czech Republic, Poland, Russia and Israel have been initiated. Affimed intends to provide a progress update on the study in the first half of 2017.

· In Affimed’s Phase 1 study in non-Hodgkin lymphoma (NHL) for AFM11, several additional trial sites were opened throughout 2016 and the trial is ongoing and recruiting. The Company continues to expect providing a progress update in the first half of 2017.
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· In July 2016, an IND for the tetravalent bispecific CD33/CD3-targeting antibody AMV564, a molecule developed from Affimed’s TandAb platform, became effective. AMV564 is being developed by Amphivena Therapeutics, Inc. and Amphivena has announced its intent to initiate a Phase 1 dose escalation clinical trial for AMV564 in patients with acute myeloid leukemia (AML). Together with the existing investor consortium, Affimed is financially supporting the clinical development of AMV564.

· Affimed has successfully generated and preclinically investigated T-cell engagers specifically binding MHC-peptide complexes. In preclinical studies, lead candidates showed selective potent in vitro killing of tumor cells endogenously expressing the targeted MHC-peptide complex. Affimed plans to provide an update on this program at the upcoming AACR (Free AACR Whitepaper) Annual Meeting in early April 2017.

Financial Highlights
(Figures for the fourth quarter of 2016 and 2015 represent unaudited figures)

Cash and cash equivalents and financial assets totaled €44.9 million as of December 31, 2016 compared to €76.7 million as of December 31, 2015. The decrease was primarily attributable to Affimed’s operational expenses.

Net cash used in operating activities for the fourth quarter of 2016 was €6.6 million compared to €4.0 million for the fourth quarter of 2015. Net cash used in operating activities was €32.1 million for the twelve months ended December 31, 2016 compared to €18.5 million for the twelve months ended December 31, 2015. The year-over-year increase was primarily related to higher cash expenditure for research and development (R&D) in connection with our development and collaboration programs.

Revenue for the fourth quarter of 2016 was €1.4 million compared to €1.7 million for the fourth quarter of 2015. Revenue for the full year 2016 was €6.3 million compared to €7.6 million for the full year 2015. Revenue in both periods was primarily derived from Affimed’s collaborations with Amphivena and the LLS as well as from third party services rendered by AbCheck.

R&D expenses for the fourth quarter of 2016 were €5.7 million compared to €7.0 million for the fourth quarter of 2015. For the full year 2016, R&D expenses were €30.2 million compared to €22.0 million for the full year 2015. The increase was primarily related to higher expenses for AFM13, AFM11, preclinical programs and infrastructure.

G&A expenses for the fourth quarter of 2016 were €2.1 million compared to €2.0 million for the fourth quarter of 2015. For the full year 2016, G&A expenses were €8.3 million compared to €7.5 million for the full year 2015. The increase was primarily related to higher share-based payment expenses.

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Net loss for the fourth quarter of 2016 was €5.4 million, or €0.16 per common share, compared to a net loss of €6.3 million, or €0.19 per common share, for the fourth quarter of 2015. Net loss for the full year 2016 was €32.2 million, or €0.97 per common share, compared to a loss of €20.2 million, or €0.71 per common share, for the full year 2015. The increase in net loss for the full year 2016 was primarily related to increased spending on R&D for AFM13, AFM11, preclinical programs and infrastructure. In addition, the result was affected by lower revenue and lower finance income. Additional information regarding these results is included in the notes to the consolidated financial statements as of December 31, 2016 and "Item 5. Operating and Financial Review and Prospects," which will be included in Affimed’s Annual Report on Form 20-F as filed with the SEC.

Including the proceeds from the offering in January and February 2017, the Company’s operations, including clinical development and early development activities, are expected to be funded at least until the end of 2018.

Note on IFRS Reporting Standards

Affimed prepares and reports the consolidated financial statements and financial information in accordance with International Financial Reporting Standards (IFRS) as issued by the International Accounting Standards Board (IASB). None of the financial statements were prepared in accordance with Generally Accepted Accounting Principles (GAAP) in the United States. Affimed maintains its books and records in Euro.

On March 30, 2017 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported that the University of Texas MD Anderson Cancer Center initiated a Phase 2 trial of poziotinib in non-small cell lung cancer patients with EGFR exon 20 insertion mutations (Press release, Spectrum Pharmaceuticals, MAR 30, 2017, View Source [SID1234518339]). This Phase 2 trial will evaluate Objective Response Rate (ORR) as the primary endpoint and is expected to yield preliminary results before year-end.

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"We are excited to be collaborating with a prominent institution to continue to develop our potential best-in-class, novel, pan-HER inhibitor, poziotinib," said Rajesh C. Shrotriya, M.D., Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "Tumors with exon 20 mutations have generally not been responsive to several other EGFR inhibitors. However, poziotinib, due to its unique structure and characteristics, is hypothesized to inhibit cell growth of EGFR exon 20 insertions. Preclinical results from poziotinib are very encouraging, and poziotinib has the potential to be a transforming therapy for these patients who have few or no options and poor prognosis. We look forward to working closely with MD Anderson Cancer Center on this study."

"Patients who suffer from this rare cancer have very few options for treatment and a poor prognosis with median progression free survival (PFS) of less than 2 months," said John Heymach, M.D., Ph.D., Chairman, Professor, and David Bruton Junior Chair in Cancer Research, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center. "Recently we saw promising preclinical results from poziotinib and based on our preclinical studies, drug screening, and computational modeling, we believe that poziotinib could potentially overcome steric hindrance of the drug binding pocket induced by the exon 20 insertion mutations. We have already seen encouraging results in a patient with this mutation who was recently treated with poziotinib on a compassionate basis. We look forward to further results from this trial later this year."

About Poziotinib

Poziotinib is a novel, oral pan-HER inhibitor that irreversibly blocks signaling through the Epidermal Growth Factor Receptor (EGFR, HER) Family of tyrosine-kinase receptors, including HER1 (erbB1; EGFR), HER2 (erbB2), and HER4 (erbB4), and importantly, also HER receptor mutations; this, in turn, leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer. Currently, poziotinib is being investigated by Hanmi in several mid-stage trials in different solid tumor indications including HER2-positive breast cancer. (Phase 2 sponsored by National OncoVenture, a funding initiative by the Korean government’s National Cancer Center).

On March 30, 2017 Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX), an oncology company developing innovative medicines and other products for targeting and treating cancer, reported that the Company’s registrational Phase 2b trial of its novel radiotherapeutic candidate, AZEDRA (iobenguane I 131) Injection, has achieved its primary endpoint (Press release, Progenics Pharmaceuticals, MAR 30, 2017, View Source [SID1234518338]). The open-label, multi-center study was conducted under a Special Protocol Assessment (SPA) agreement with the Food and Drug Administration (FDA). The trial was designed to evaluate the efficacy and safety of AZEDRA in patients with malignant and/or recurrent pheochromocytoma or paraganglioma, which are rare neuroendocrine tumors. There are currently no approved therapeutics in the U.S. for the treatment of malignant and/or recurrent pheochromocytoma or paraganglioma. AZEDRA has received Breakthrough Therapy, Orphan Drug and Fast Track designations from the FDA.

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The study met the primary endpoint evaluating the proportion of patients who achieved a 50% or greater reduction of all antihypertensive medication for at least six months. Under the study protocol, the primary endpoint is achieved if the lower limit of the two-sided 95% confidence interval was above 10%.

In the trial, 17 (25%) of the 68 evaluable patients experienced a 50% or greater reduction of all antihypertensive medication for at least 6 months. The lower limit of the 95% confidence interval was 16.15%, thus meeting the primary endpoint. The upper limit of the 95% confidence interval was 36.52%.

Progenics also reported favorable data from a key secondary endpoint, the proportion of patients with overall tumor response as measured by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. In this highly pre-treated patient population, 92.2% of patients who received at least one AZEDRA therapeutic dose achieved partial response or stable disease.

"The positive data from this trial are clinically meaningful and provide compelling evidence for the use of AZEDRA to treat malignant and/or recurrent pheochromocytoma and paraganglioma," said Dr. Daniel Pryma, Associate Professor of Radiology & Radiation Oncology and Chief, Division of Nuclear Medicine & Clinical Molecular Imaging at the Perelman School of Medicine at the University of Pennsylvania, the trial’s lead investigator. "Without any approved therapeutics in the U.S. for these rare and devastating life-threatening tumors, patients face a poor prognosis and few options. The tumor response data, in particular for the patients that received two doses, along with the adverse event profile from this trial, suggest that AZEDRA has the potential to be a true breakthrough in addressing these difficult-to-treat patients."

Phase 2b Trial Topline Results
The Phase 2b open-label trial was designed to evaluate the efficacy and safety of two therapeutic doses of AZEDRA administered three months apart to patients with malignant relapsed/refractory pheochromocytoma or paraganglioma.

Primary Endpoint: Reduction in Antihypertensive Medications
Under the study protocol, the primary endpoint is achieved if the lower limit of the two-sided 95% confidence interval was above 10%. In order to achieve this primary endpoint, a minimum of 12 of the total 68 evaluable patients must have a 50% or greater reduction of all antihypertensive medication for at least 6 months. As shown in the table below, 17 patients responded, giving a lower limit of the 95% confidence interval of 16.15%, thus meeting the primary endpoint.

Responders (%) Lower bound of
Confidence Interval Upper bound of
Confidence Interval
Overall
(n=68) 17 (25%)

16.15

%

36.52

%

Two Doses
(n=50) 16 (32%)

20.70

%

45.87

%

One Dose
(n=18) 1 (5.6%)

0.0

%

27.65

%



Secondary Endpoint: Overall Tumor Response Assessment per RECIST Criteria
Best response over 12 months after first therapeutic dose

Complete
Response Partial
Response Stable Disease

Progressive
Disease Unable to
Evaluate
Overall
(n=64*) 0

%

23.4

%

68.8

%

4.7

%

3.1

%

2 doses
(n=50) 0

%

30.0

%

68.0

%

2.0

%

0

%

1 dose
(n=14) 0

%

0

%

71.4

%

14.3

%

14.3

%

*4 patients did not have follow-up scans

AZEDRA was generally well tolerated. The most common treatment emergent adverse events were nausea, thrombocytopenia, anemia, fatigue, leukopenia, and neutropenia. These events are consistent with those observed in prior AZEDRA studies.

"We intend to move quickly to complete our New Drug Application submission by mid-2017, as these topline results underscore the potential of AZEDRA in this ultra-orphan indication," said Mark Baker, Chief Executive Officer of Progenics. "We are grateful to the patients and investigators who participated in this trial, and are committed to bringing a new treatment option to this rare cancer population."

Progenics plans to present additional data from this trial at a medical meeting in the second half of 2017.

On March 30, 2017 Merrimack Pharmaceuticals, Inc. (NASDAQ: MACK) ("Merrimack") reported that, at its Special Meeting of Stockholders held today, its stockholders voted to approve the asset sale with Ipsen S.A (Press release, Merrimack, MAR 30, 2017, View Source [SID1234518337]).

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Merrimack will:
Sell to Ipsen its first commercial product ONIVYDE, including U.S. commercialization rights and its licensing agreement with Shire plc; and

Sell to Ipsen its generic version of doxorubicin hydrochloride (HCI) liposome injection ("generic DOXIL") marketed in the United States as DOXIL and advanced under a development, license and supply agreement with Actavis LLC.

Richard Peters, M.D., Ph.D., Merrimack’s President and Chief Executive Officer, said, "I would like to thank our stockholders for their strong support. This compelling transaction will deliver significant and immediate cash value for stockholders while also providing them with the opportunity to participate in the significant potential upside of Merrimack. We are excited to move forward as a more focused, well-funded research and development company targeting three highly promising clinical stage assets, MM-121, MM-141 and MM-310. We will continue to work closely with Ipsen to complete the transaction and achieve a smooth transition."

Merrimack expects the transaction to be completed in the coming days.