On June 27, 2017 Affimed N.V. (Nasdaq: AFMD), a clinical stage biopharmaceutical company focused on discovering and developing highly targeted cancer immunotherapies, reported the presentation of preclinical data for the Company’s AFM24 and AFM26 programs at the EACR-AACR-SIC 2017 Special Conference in Florence, Italy (Press release, Affimed, JUN 27, 2017, View Source [SID1234519711]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"With our NK-cell engagers AFM24 and AFM26 we are pursuing two preclinical programs which we believe are ideally suited to exploit NK-cell mediated cytotoxicity to fight cancer," said Dr. Martin Treder, Chief Scientific Officer of Affimed. "Our data for both programs show a well-differentiated profile from competitor products, addressing the need for higher efficacy and better safety."

AFM24 and AFM26 are two first-in-class tetravalent, bispecific NK-cell engagers targeting CD16A, a dominant activating receptor on NK-cells. In addition, AFM24 targets EGFR, while AFM26 binds to BCMA. Corroborating the Company’s earlier data, the studies presented at EACR-AACR-SIC 2017 provided further evidence of favorable safety profiles for both NK-cell engagers and also confirmed their ability to potently and effectively lyse tumor cells, even those with very low target expression. Furthermore, the high affinity to CD16A on NK-cells, resulting in long cell retention binding to NK-cells, and the minimal influence of serum IgG on tumor cell lysis are important differentiating factors of Affimed’s NK-cell platform compared to IgG-based monoclonal antibodies (mAbs).

In detail, AFM24 was shown to be distinguished from cetuximab in vitro and in vivo through higher potency at both high and low EGFR expression levels and in RAS mutant cells, while offering a more favorable safety profile. Single and repeat dose toxicology studies in cynomolgus monkeys demonstrated that AFM24 was well-tolerated at high doses. Further differentiating AFM24 from other therapies, no evidence of skin toxicity, a side effect commonly seen for other anti-EGFR antibodies and for tyrosine kinase inhibitors, was observed.

In addition, the Company presented further data highlighting the preclinical progress of AFM26. The NK-cell engager was able to elicit efficient tumor cell lysis in both cell lines and primary cells, even at very low BCMA expression levels. In addition, the amount of inflammatory cytokines released in vitro by cells treated with AFM26 was markedly lower than those of cells treated with a BCMA/CD3 T-cell engager. Furthermore, in contrast to approved mAb therapies such as daratumumab and elotuzumab, AFM26 did not induce NK-cell depletion in vitro.

Taken together, the results presented at EACR-AACR-SIC 2017 support the therapeutic rationale of redirecting NK-cells to tumors through bispecific tetravalent NK-cell engagers, which offers a novel mode of action addressing limitations of other therapies.

On June 26, 2017 Oxis International Inc. (OTCQB: OXIS) and (Euronext Paris: OXI.PA) reported that it has executed a binding LOI agreement to acquire Georgetown Translational Pharmaceuticals, Inc. (GTP), a deal that will add new management and a class of close-to-market Central Nervous Systems (CNS) products that will add significant value to the Oxis business model (Press release, OXIS International, JUN 26, 2017, View Source [SID1234539561]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Oxis has agreed to pay 33 percent of its outstanding shares to GTP to complete the transaction, which is expected to close on or before 90 days as per the agreement.

GTP, founded by Kathleen Clarence-Smith, MD, PhD, and Mark J. Silverman, JD, was incorporated in Delaware in 2015.

Dr. Clarence-Smith will become Chief Executive Officer of Oxis as part of the acquisition and will be appointed to the Oxis Board of Directors. Also joining the company’s executive management team as part of the merger will be a Chief Medical Officer (name to be disclosed upon closing), who was formerly Vice President and Chief Medical Officer and Medical Director, Oncology Clinical R&D of Pfizer, Inc. (PFE).

Anthony J. Cataldo, who has served as Chief Executive Officer of Oxis since July 2014, will become Executive Chairman of the company. Steven Weldon will continue as Chief Financial Officer.

Prior to founding GTP, Dr. Clarence-Smith co-founded Chase Pharmaceuticals Corporation in Washington D.C. and served as Chairman of the company’s Board from 2008 to 2014. Chase Pharmaceuticals was acquired by Allergan, PLC (AGN) in 2016.

Under the deal, Allergan agreed to pay $125 million upfront along with potential Regulatory and commercial milestones of up to $875 million to the shareholders of Chase.

View Source

Dr. Clarence-Smith also held executive management positions with Sanofi, Roche, Otsuka Pharmaceutical and Prestwick Scientific Capital. She is co-founder and a managing member of KM Pharmaceutical Consulting in Washington, D. C.

"The merger of Oxis and GTP will greatly accelerate the clinical development of exciting new treatments to meet the medical needs of those suffering from cancer and neurologic disease," said Dr. Clarence-Smith. "Harnessing the immune system to fight cancer has the potential to soon bring the cure for certain cancers within our reach, and our CNS pipeline includes drugs that have the potential to improve the quality of life of many patients."

Oxis’ incoming CMO said: "The drugs in the Oxis pipeline are at the forefront of targeted immunotherapeutics and represent the wave of the future. The non-clinical and clinical data is impressive and validates this approach to cancer therapy. Once approved, these agents will herald a major breakthrough in the field of immunotherapy and offer patients hope against some of the most difficult diseases to treat."

Mr. Cataldo said: "The addition of Dr. Clarence-Smith as CEO and our new incoming CMO will be instrumental in completing Oxis’ FDA phase 2 clinical trial of OXS-1550 and our plans to advance the highly-valued TriKE platform oncology assets, which are set to go into FDA clinical trials soon. Further, we are very excited with the incoming GTP product pipeline, which will add significant value as they continue to move towards a commercial license."

Oxis’ lead drug candidate, OXS-1550 (DT2219ARL), is a novel drug that binds to targets and destroys cancer cells, due to the action of the drug’s cytotoxic payload. OXS-1550 has demonstrated success in early human clinical trials in patients with relapsed/refractory B-cell lymphoma or leukemia. It is currently in a FDA-approved Phase 2 trial at the University of Minnesota.

In addition, Oxis holds the rights to commercialize OXS-3550, also known as TriKE, a targeted immunotherapy platform drug that directs Natural Killer (NK) cells to kill cancer cells without drug-related toxicity. "The first molecule called 161533 TriKE will target the CD33 antigen on acute myeloid leukemia cells. The 161533 TriKE will enable NK cells to become antigen specific and also drive the immune response through its IL-15 linker. Our existing Oncology products have now reached the point where Dr. Clarence-Smith’s experience in taking drugs through FDA approvals and into the market, will bring significant value to our shareholders," Mr. Cataldo said.

The agreement to acquire GTP marks another major value-added inflection point for the shareholders of Oxis. The company continues to progress with recently announced partnership and milestone accomplishments.

On June 26, 2017 Advaxis, Inc. (NASDAQ:ADXS), a late-stage biotechnology company developing cancer immunotherapies, reported that the European Society of Gynaecologic Oncology (ESGO) has accepted an abstract for a poster presentation at its 2017 congress on the identification of potential baseline biomarkers indicative of survival benefit from treatment with the company’s lead immunotherapy candidate, axalimogene filolisbac (Press release, Advaxis, JUN 26, 2017, View Source [SID1234519687]). ESGO is Europe’s landmark gynecologic oncology meeting. Held biennially, ESGO congress brings together professionals to learn and discuss the latest medical and scientific developments in gynecologic cancers research, treatment and care.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Know more, wherever you are:
Latest on Immuno-Oncology, book your free 1stOncology demo here.

Advaxis researchers identified certain pre-treatment baseline levels of serum proteins that were strongly associated with overall survival (OS) benefit in patients with persistent or recurrent metastatic carcinoma of the cervix (PRmCC) that were treated with axalimogene filolisbac in the Phase 2 GOG/NRG-0265 study. The 12-month survival rate in this study was 38 percent (19/50), and these results were presented at a medical meeting earlier this year.

This analysis of pre-treatment baseline serum proteins of 45 patients from the study showed that levels of a group of four closely-aligned proteins were strongly correlated with OS. One cluster of patients (n=25), had relatively lower levels of all four proteins and exhibited an OS of 56 percent, while the second cluster (n=20), with relatively higher levels, exhibited an OS of 15 percent. These data are statistically significant (HR=0.23; 95% CI: 0.10-0.48; P<.001) and suggest that the baseline levels of these analytes have prognostic value for OS, and high levels of these individual proteins were negatively associated with clinical outcomes in the trial.

Importantly, it was found that much of this effect was due to levels of one particular protein, which was found to be most highly correlated with OS in the study. This particular protein was previously not known to be associated with survival in cervical cancer. Advaxis will continue to evaluate this particular protein as a potential biomarker to help identify patients most likely to benefit from treatment with axalimogene filolisbac.

"In the field of cancer immunotherapy, biomarkers have been playing an increasing role in guiding patient selection and identifying early indicators of treatment response," said Robert Petit, Chief Scientific Officer of Advaxis. "The discovery of this potential biomarker, which previously has not been known to be associated with survival in cervical cancer, is significant and could be a biomarker to predict efficacy, similar to how PD-L1 expression is used as a biomarker for checkpoint inhibitors. PD-L1 testing has become an important and routine strategy to guide treatment, and this biomarker has the promise to do the same for axalimogene filolisbac."

Sandy Hayes, PhD, Associate Director of Research and Biomarker Lead at Advaxis, is the first author and presenter of "Baseline Serum Protein Levels Associated with Survival in Axalimogene Filolisbac (Axal)-Treated Metastatic Cervical Cancer Patients: The GOG/NRG-0265 Trial." The poster will be presented at ESGO 2017, held Nov. 4 to 7 in Vienna, Austria, and will also be published in a supplement to the International Journal of Gynecological Cancer.

About Cervical Cancer

Cervical cancer is the fourth most common cancer affecting women worldwide. An estimated 13,000 cases were diagnosed in the United States in 2016, and 4,100 women will have this disease as their cause of death each year, according to the National Cancer Institute. Decades of research have shown that persistent HPV infection, particularly with high-risk virus types such as HPV-16 and HPV-18, is the most important factor in the development of cervical cancer. The prognosis for women with advanced and recurrent cervical cancer remains poor, with median survival of only six to seven months following initiation of palliative treatment with chemotherapy. According to the American Cancer Society, the five-year survival rate for stage IV disease is at 15 to 16 percent. There is no approved therapy following failure of first-line treatment, and there has been limited advancement in developing new therapeutics for advanced cervical cancer over the last 30 years.

About Axalimogene Filolisbac

Axalimogene filolisbac is a targeted Listeria monocytogenes (Lm)-based immunotherapy that attacks HPV-associated cancers by altering a live strain of Lm bacteria to generate cancer-fighting T cells against cancer while neutralizing the tumor’s natural protections that guard the tumor microenvironment from immunologic attack.

Axalimogene filolisbac has received Fast Track designation as an adjuvant therapy for high-risk locally advanced cervical cancer (HRLACC) patients and a Special Protocol Assessment for the Phase 3 AIM2CERV trial in HRLACC patients. Axalimogene filolisbac is the only active product candidate to have received the U.S. FDA orphan drug designation in cervical cancer.

Advaxis, in collaboration with Bristol-Myers Squibb, is evaluating ADXS-DUAL, the next generation immunotherapy candidate targeting HPV-associated cancers, with the PD-1 immune checkpoint inhibitor, Opdivo (nivolumab), as a potential combination treatment option for women with metastatic cervical cancer. Expected to start by the end of 2017, the study will evaluate this combination regimen in women with PRmCC who have failed at least one prior line of systemic chemotherapy.

On June 25, 2017 AOP Orphan Pharmaceuticals AG (AOP Orphan) and PharmaEssentia Corporation (Taipei Exchange: 6446) announced latest results from 3 clinical studies on Ropeginterferon alfa-2b for patients with Polycythemia Vera (PV) presented at EHA (Free EHA Whitepaper) 2017 (Press release, AOP Orphan Pharmaceuticals, JUN 25, 2017, View Source [SID1234519690]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Ropeginterferon alfa-2b is a novel, long-acting, mono-pegylated proline interferon expected to be the first interferon approved for PV worldwide. It is currently under EMA review for marketing authorization in the EU by AOP Orphan, PharmaEssentia intends to seek its approval by the FDA in the U.S.

Abstract EHA (Free EHA Whitepaper)-3520: An update from the PEGINVERA study (NCT: 2010-018768-18) on long-term maintenance treatment of up to 6 years (median of 4 years) with Ropeginterferon alfa-2b was provided. Patients were successfully switched from the once every 2 weeks to the more convenient once every 4 weeks’ long-term maintenance dosing schedule after a median of approximately 2 years.

All 29 patients could be maintained on this schedule for another 2 years, representing 100% treatment adherence. The high rates of hematological (over 80% of the patients achieved partial or complete hematologic response) and molecular responses (up to 80% of the patients achieved partial or complete molecular response) were maintained after the switch to the 4 weeks’ schedule and remain stable (trial still ongoing).

After 4 years on Ropeginterferon alfa-2b, the majority of patients showed a sustained reduction of the mutant JAK2V617F allelic burden to below 10%, demonstrating the disease modifying capability of Ropeginterferon alfa-2b treatment.

No disease progression was reported.

Abstract EHA (Free EHA Whitepaper)-3556: To alleviate the known burden of frequent health care office visits for product administration, home self-administration and patient individual dosing of Ropeginterferon alfa-2b were performed in the PEN-PV study (NCT: 2014-001356-31).

Based on investigator assessments, none of the 36 patients exhibited any visible pain or physical discomfort, nor did any patient report pain arising from the use of the pen. The Ropeginterferon alfa-2b pen was well accepted by patients and health care professionals, hematological parameters and spleen size remained stable throughout the study and there were no safety concerns.

The pen allows for individual dosing and patient-convenient self-administration at home. It is expected to support adherence to Ropeginterferon alfa-2b in the long-term treatment of PV-patients.

Abstract EHA (Free EHA Whitepaper)-1564: To assess the disease modifying capability of Ropeginterferon alfa-2b compared to hydroxyurea (HU), the effect of treatment on hematopoietic bone marrow progenitor cells was investigated in 10 patients of the French PROUD-PV study population (NCT01949805).

Although at 12 months, both drugs led to a decrease of the mutant JAK2V617F allelic burden in peripheral blood, only Ropeginterferon alfa-2b induced a meaningful decrease of mutated hematopoietic bone marrow progenitor cells (median decrease 64% compared to only 25% under HU).

Professor Jean-Jacques Kiladjian from the Saint-Louis Hospital & Paris Diderot University in France, who presented the results on molecular responses of Ropeginterferon alfa-2b on hematopoietic progenitor cells at EHA (Free EHA Whitepaper), stated "Results from this study further support the potential for long-term patient benefits, including progression-free survival and underscore the unique disease modification capabilities of Ropeginterferon alfa-2b."

About Ropeginterferon alfa-2b

Ropeginterferon alfa-2b is a novel, long-acting, mono-pegylated proline interferon with improved pharmacokinetic properties offering improved tolerability and convenience. Ropeginterferon alfa-2b was discovered by PharmaEssentia. Ropeginterferon alfa-2b has Orphan Drug designation in the European Union and the United States of America. PharmaEssentia plans to commercialize ropeginterferon alfa-2b in North and South America, as well as Asia. PharmaEssentia has exclusively licensed the rights for Ropeginterferon alfa-2b to AOP Orphan for European, Commonwealth of Independent States (CIS), and Middle Eastern markets for the development and commercialization in the field of Myeloproliferative Neoplasms (MPNs).

About Polycythemia Vera

Polycythemia Vera (PV) is a cancer of the blood-building cells in the bone marrow resulting in a chronic increase of red blood cells, white blood cells and platelets. This condition may result in circulatory disorders such as thrombosis and embolism, as well as malignant transformation to myelofibrosis or leukemia.

On June 23, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the US Food and Drug Administration (FDA) approved Rituxan Hycela (rituximab and hyaluronidase human) for subcutaneous (under the skin) injection, for the treatment of adults with the following blood cancers: previously untreated and relapsed or refractory follicular lymphoma, previously untreated diffuse large B-cell lymphoma (DLBCL), and previously untreated and previously treated chronic lymphocytic leukaemia (CLL) (Press release, Hoffmann-La Roche, JUN 23, 2017, View Source [SID1234519669]). This new treatment includes the same monoclonal antibody as intravenous Rituxan (rituximab) in combination with hyaluronidase human, an enzyme that helps to deliver rituximab under the skin.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"With today’s approval of Rituxan Hycela, people with three of the most common blood cancers now have a new treatment option which provides efficacy comparable with intravenous Rituxan and can be delivered under the skin in minutes instead of hours through IV infusion," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "People who benefit from Rituxan may receive years of repeated treatments for their blood cancer, so an option that reduces the administration time can be important."

The FDA approval is based on results from clinical studies, which demonstrated that subcutaneous administration of Rituxan Hycela resulted in non-inferior levels of rituximab in the blood (pharmacokinetics) and comparable clinical efficacy outcomes compared to intravenous Rituxan. One of the studies showed the majority (77%) of patients preferred Rituxan Hycela over intravenous Rituxan, with the most common reason being that administration required less time in the clinic. People can only receive Rituxan Hycela after at least one full dose of intravenous Rituxan.

With the exception of local skin (cutaneous) reactions, the incidence and profile of adverse reactions for Rituxan Hycela were comparable with those for intravenous Rituxan. The most common (≥20%) adverse reactions observed with Rituxan Hycela in people with follicular lymphoma were infections, low white blood cell count (neutropenia), nausea, constipation, cough and fatigue. The most common adverse reactions in people with DLBCL were infections, neutropenia, hair loss (alopecia), nausea and low red blood cell count (anemia). The most common adverse reactions in people with CLL were infections, neutropenia, nausea, low platelet count (thrombocytopenia), fever (pyrexia), vomiting and reddening of the skin (erythema) at the injection site.

Rituxan Hycela will be available to people in the United States within one to two weeks, and intravenous Rituxan will continue to be available.

About the Rituxan Hycela Clinical Development Program
The approval of Rituxan Hycela is based on results from clinical studies that together represented nearly 2,000 people. The studies were the following:
SABRINA (NCT01200758): Phase III combination with chemotherapy and maintenance study in previously untreated follicular lymphoma

SAWYER (NCT01292603): Phase Ib study in previously untreated chronic lymphocytic leukaemia (CLL)
MabEase (NCT01649856): Phase III study in previously untreated diffuse large B-cell lymphoma (DLBCL)
PrefMab (NCT01724021): Phase III patient preference study in previously untreated follicular lymphoma and DLBCL

About MabThera/Rituxan (rituximab)
MabThera/Rituxan is a therapeutic monoclonal antibody that binds to a particular protein – the CD20 antigen – on the surface of normal and malignant B-cells. It then recruits the body’s natural defenses to attack and kill the marked B-cells. Stem cells (B-cell progenitors) in bone marrow lack the CD20 antigen, allowing healthy B-cells to regenerate after treatment and return to normal levels within several months.

Rituxan first received FDA approval for the treatment of relapsed indolent non-Hodgkin Lymphoma (NHL) in 1997 and was the first targeted cancer medicine approved by the U.S. Food and Drug Administration (FDA). MabThera was approved in the EU in June 1998, and has since been used to treat more than 2.7 million people with specific blood cancers. For more than 15 years, the efficacy and safety of MabThera/Rituxan has been documented in more than 300 phase II/III clinical studies. MabThera/Rituxan has been approved for the treatment of several blood cancers, specifically, certain types of NHL and for chronic lymphocytic leukaemia (CLL). It continues to be studied in other types of blood cancers and disease areas where CD20-positive cells are believed to play a role.

MabThera is known as Rituxan in the United States, Japan and Canada. Genentech, a member of the Roche Group, and Biogen collaborate on Rituxan in the United States, and Roche markets MabThera in the rest of the world, except Japan, where MabThera is co-marketed by Chugai and Zenyaku Kogyo Co. Ltd.

About Rituxan Hycela
Rituxan Hycela is a co-formulation of the same monoclonal antibody as intravenous MabThera/Rituxan and Halozyme Therapeutics’ proprietary hyaluronidase human, an FDA-approved enzyme that facilitates the delivery of a large volume of medicine under the skin. Rituxan Hycela can be administered in five to seven minutes, compared to 1.5 to four hours for intravenous MabThera/Rituxan. It is known as the subcutaneous (SC) formulation of MabThera (rituximab) in the European Union.

About Follicular Lymphoma
Follicular lymphoma is the most common indolent (slow-growing) form of non-Hodgkin lymphoma (NHL), accounting for about one in five cases of NHL1. It is considered incurable and relapse is common. Every day, more than 50 people in Europe are diagnosed this type of NHL2. It is estimated that each year, more than 75,000 people are diagnosed with follicular lymphoma worldwide2.

About Diffuse Large B-Cell Lymphoma (DLBCL)
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for about one in three cases of NHL3. DLBCL is an aggressive (fast-growing) type of NHL, which is generally responsive to treatment in the frontline4. However, as many as 40% of patients will relapse, at which time salvage therapy options are limited and survival is short4. Approximately 123,000 people worldwide are estimated to be diagnosed with DLBCL each year5.

About Chronic Lymphocytic Leukaemia (CLL)
Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in the Western world6. CLL mainly affects men and the median age at diagnosis is about 70 years7. Worldwide, the incidence of all leukaemias is estimated to be over 350,0006 and CLL is estimated to affect around one-third of all people newly diagnosed with leukaemia8.