On October 8, 2018 Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) ("Navidea" or the "Company"), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, reported that its Chief Executive Officer, Jed Latkin, will present a corporate overview of the Company at the 2018 BIO Investor Forum, being held October 17-18, 2018 in San Francisco, California (Press release, Navidea Biopharmaceuticals, OCT 8, 2018, View Source [SID1234530337]).

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Conference Presentation Details:

Where: The Westin St. Francis Hotel, San Francisco, California
When: Thursday, October 18, 2018 at 11:15AM PDT
Room: Elizabethan C
Conference Website:
View Source

To schedule a meeting, investors can submit meeting requests through the conference one-on-one partnering system.

On October 8, 2018 Affimed N.V. (Nasdaq: AFMD), a clinical stage biopharmaceutical company focused on discovering and developing highly targeted cancer immunotherapies that harness the power of innate and adaptive immunity (NK and T cells), reported that it has placed AFM11 (CD19/CD3-targeting T cell engager) on clinical hold, and has notified the global health authorities of its decision (Press release, Affimed, OCT 8, 2018, View Source [SID1234530285]). AFM11 is being evaluated in two Phase 1 clinical studies for the treatment of patients with relapsed or refractory CD19 positive B-cell non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL). The clinical hold was initiated after the occurrence of Serious Adverse Events (SAEs) in three patients, which included a death in the ALL study and two life-threatening events in the NHL study.

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The SAEs occurred in patients enrolled in the highest dose cohorts of each study. Thirty-three patients have been treated in total in the two Phase 1 studies, with preliminary signs of clinical activity observed in several patients.

Affimed will be working closely with the global health authorities, the Safety Monitoring Committees, and the studies’ clinical investigators to review the events, carefully assess all of the data and determine next steps for the AFM11 program. Affimed intends to provide an update on AFM11 upon completion of the evaluation.

The clinical hold does not affect the ongoing development of Affimed’s NK cell engager programs, which are based on targeting the NK cell receptor CD16A, a different approach than used for AFM11, which targets T cells through CD3.

On October 8, 2018 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported the successful animal testing of DNA-encoded monoclonal antibodies targeting the immune checkpoint molecule CTLA-4 as published in Cancer Research (Press release, Inovio, OCT 8, 2018, View Source;Monoclonal-Antibody-dMAb-Checkpoint-Inhibitor–and-Demonstrates-Tumor-Shrinkage-in-Preclinical-Studies/default.aspx [SID1234530270]). The breakthrough preclinical study demonstrated that highly optimized dMAbs targeting mouse CTLA-4 protein can be robustly expressed in vivo, and shrank tumors in mice. More importantly, Inovio’s dMAb constructs for anti-human CTLA-4 antibodies ipilimumab (YERVOY) and tremelimumab, achieved high expression levels in mice (approximately 85µg/ml and 58µg/ml, respectively). These dMAbs exhibited long-term expression with maintenance of serum levels >15µg/ml for over a year.

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This research publication is significant because it is the first to report on the use of Inovio dMAb technology to develop novel monoclonal antibody-based therapies targeting checkpoint inhibitors. Inovio is developing additional dMAbs targeting other checkpoint molecules including PD-1. When delivered directly into the body, the genetic instructions provided from the dMAb construct enable the patient’s own cells to become the factory which manufactures the therapeutic monoclonal antibody products. Inovio has previously published several papers demonstrating its dMAb product candidate’s ability to treat multiple virus targets such as flu, dengue, chikungunya, and HIV.

Laurent Humeau, Ph.D., Inovio’s Senior Vice President, Research & Development, said, "Even though conventional monoclonal antibodies represent one of the most successful segments of the biotechnology market, accounting for over $50 billion in sales today, manufacturing complexity and repeated dosing may limit a broader use of this technology. Inovio’s dMAb products may improve upon this class using our synthetic design and in vivo production. This newly published study further support that Inovio’s potent dMAb platform can be expanded to target cancer. We plan on advancing the first clinical dMAb candidate into the first-in-human study in 2019. Moreover, we expect to form partnerships to advance several dMAb products targeting cancers and infectious diseases."

David B. Weiner, Ph.D., the paper’s senior author and the W.W. Smith Charitable Trust Professor in Cancer Research at The Wistar Institute, said, "Our work provides the first demonstration that we can use synthetic DNA technology to produce checkpoint inhibitor molecules in vivo to impact tumor growth in a preclinical setting. We showed that dMAbs may represent a valuable addition to the cancer immunotherapy toolbox: In our preclinical studies, dMAbs achieved antitumor activity comparable to that of traditional monoclonal antibodies, while being delivered through a simpler formulation that may provide a bridge to expand target populations for checkpoint inhibitors."

The study highlights that delivery of a synthetic, sequence-optimized DNA plasmid designed to encode anti-mouse CTLA-4 monoclonal antibodies, with the aid of an electroporation device to enhance uptake, resulted in significant and prolonged antibody expression with even a single dose. Importantly, this approach stimulated robust CD8+ T cell infiltration, achieving tumor clearance across multiple mouse tumor models. The researchers then went on to develop human checkpoint inhibitor molecules and demonstrated their production in mice and their ability to stimulate human T cell responses associated with antitumor activity. The study clearly demonstrates how optimized dMAbs encoding the human CPI’s ipilimumab and tremelimumab are potently expressed in vivo and enhance the activation of human effector T cells with the potential to destroy tumors. This strategy provides a novel approach to immune checkpoint therapy, with the potential to expand patient access to this breakthrough immunotherapy to treat cancer.

Funded with over $60 million in R&D support from top agencies like DARPA, NIH, and the Gates Foundation, Inovio dMAb products could extend the medical benefits that marketed monoclonal antibodies have already achieved, and even potentially address diseases that conventional monoclonal antibodies cannot.

About Inovio’s DNA-based Monoclonal Antibody Platform

Traditional monoclonal antibodies are manufactured outside the body in bioreactors, typically requiring costly large-scale manufacturing facility development and laborious production. Inovio’s disruptive dMAb technology has the potential to overcome these limitations by virtue of their simplified design, rapidity of development, product stability, ease of manufacturing and deplorability, and cost effectiveness, thereby providing potential new avenues for treating a range of diseases. Another significant advancement seen in Inovio dMAb technologies is that the optimized genes for a desired monoclonal antibody is encoded in a DNA plasmid, which is produced using very cost effective and highly scalable fermentation techniques. These plasmids are delivered directly into cells of the body using electroporation and the encoded monoclonal antibody is then directly produced by these cells. Previously published studies show that a single administration of a highly optimized DNA-based monoclonal antibody targeting HIV virus produced a high level of expression of the antibody in the bloodstream of mice; Inovio similarly reported data showing that dMAb products against flu, Ebola, chikungunya and dengue protected animals against lethal challenge. Inovio Ebola dMAb product is being developed under a grant from the Defense Advanced Research Projects Agency (DARPA).

On October 8, 2018 Adaptimmune Therapeutics plc ("Adaptimmune") (Nasdaq: ADAP), a leader in T-cell therapy to treat cancer, reported further details about two poster presentations at the upcoming ESMO (Free ESMO Whitepaper) congress, as follows (Press release, Adaptimmune, OCT 8, 2018, View Source;p=RssLanding&cat=news&id=2370701 [SID1234530171]):

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MAGE-A10 poster for discussion presentation details:

A late-breaking abstract with data from the two ongoing MAGE-A10 studies ("triple tumor" and lung) was accepted for poster discussion, with the full abstract and data to be made available at the time of presentation.
Title: Safety and Anti-Tumor Effects of MAGE-A10c796TCR T-cells in Two Clinical Trials (Poster #LBA38)
Poster discussion session: Immuno 1 in ICM room 14b
Time: Saturday, October 20 from 16:45 to 17:45 CEST (10:45 to 11:45 EDT)
MAGE-A4 poster presentation details:

The full abstract for the MAGE-A4 poster is now available online (https://bit.ly/2NMBC3d) and is summarized below
Title: Initial Safety Assessment of MAGE-A4 SPEAR T-cells (Poster #1156P)
Poster display session (ID 259): Immunotherapy of cancer in Hall A3 poster networking Hub
Time: Saturday, October 20 from 12:30 to 13:30 CEST (06:30 to 07:30 EDT)
Brief summary of abstract (data cut-off 25 April 2018):
Background:

Ongoing study (NCT03132922) to evaluate safety and tolerability of SPEAR T-cells directed towards a MAGE-A4 peptide expressed on tumors in the context of HLA-A*02
Methods:

Modified 3+3 design
Patients have inoperable or metastatic (advanced) non-small cell lung cancer (NSCLC), urothelial ("bladder"), melanoma, synovial sarcoma, myxoid/round cell liposarcoma (MRCLS), head & neck, ovarian, gastric, or esophageal cancers expressing MAGE-A4
Lymphodepletion regimen:
Cohorts 1, 2: [fludarabine (Flu) 30 mg/m2/day and cyclophosphamide (Cy) 600 mg/m2/day] x 3 days
Cohort 3: [Flu 30 mg/m2/day] x 4 days + [Cy 600 mg/m2/day] x 3 days
Expansion Cohort: [Flu 30 mg/m2/day] x 4 days + [Cy 600 mg/m2/day] x 3 days
Dose:
Cohort 1: target 100 million (M) transduced cells; range 80 to 120 M transduced cells
Cohort 2: target 1 billion (B) transduced cells; range 0.5 to 1.2 B transduced cells
Cohort 3: target 5 B transduced cells; range 1.2 to 6.2 B transduced cells
Expansion Cohort: target 5 B transduced cells; range 1.2 to 10 B transduced cells
Results:

Three patients were treated with 100 M MAGE-A4 SPEAR T-cells, and transduced cells were detectable in peripheral blood
Adverse events (AEs) for the first 2 patients reported at grade (G) ≥3 included anemia, hypoglycemia, hyponatremia, lymphopenia, neutropenia, and thrombocytopenia
Serious AEs included G4 hyponatremia, G3 atrial fibrillation, G3 syncope (unrelated to T-cell therapy), G1 CRS and G2 encephalopathy syndrome (both related), and G2 generalized muscle weakness (possibly related)
None of the events were considered dose limiting toxicities (DLTs) by the Safety Review Committee
Conclusions:

MAGE-A4 SPEAR T-cells at the 100 M transduced cell dose appear to show no evidence of on‑target or off-target toxicity
Preliminary data support continued investigation of the T-cell receptor (TCR), and this trial is ongoing

On October 8, 2018 Sanofi and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that it will present a diverse set of data from their joint clinical program investigating Libtayo (cemiplimab-rwlc) at the ESMO (Free ESMO Whitepaper) 2018 Congress (European Society for Medical Oncology) from October 19 to 23 in Munich, Germany (Press release, Sanofi Genzyme, OCT 8, 2018, View Source [SID1234530053]). These data span six different tumor types, including non-small cell lung cancer (NSCLC), cervical cancer, cutaneous squamous cell carcinoma (CSCC), hepatocellular carcinoma (HCC), head and neck squamous cell carcinoma (HNSCC) and basal cell carcinoma (BCC). Libtayo is a fully-human monoclonal antibody targeting the immune checkpoint receptor PD-1 (programmed cell death protein-1).

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"Following the U.S. FDA approval of Libtayo in advanced CSCC, we remain focused on pursuing science that has the potential to change treatment paradigms in oncology," said Israel Lowy, M.D., Ph.D., Vice President of Global Clinical Development and Head of Translational Science and Clinical Oncology, Regeneron. "At ESMO (Free ESMO Whitepaper), we look forward to sharing new data that support our rationale for pursuing registrational trials of Libtayo in lung, cervical and skin cancers."

All six of the abstracts accepted at ESMO (Free ESMO Whitepaper) focus on ongoing Libtayo clinical trials.

"Three years ago, Sanofi began its immuno-oncology collaboration with Regeneron with the shared vision to address significant unmet needs across various cancer types," said Joanne Lager, M.D., Head of Oncology Development, Sanofi. "This year’s data being presented at ESMO (Free ESMO Whitepaper) are a testament to our commitment to patients and the potential to make our vision a reality."

Among the joint Sanofi and Regeneron presentations are new clinical data from a Phase 1 expansion cohort investigating Libtayo in combination with radiotherapy in advanced NSCLC as well as longer-term follow-up data from the advanced CSCC expansion cohorts in the Phase 1 trial. Additional abstracts will feature initial data from Phase 1 expansion cohorts investigating Libtayo in cervical cancer, HCC and HNSCC, alongside a trial-in-progress update on the potentially pivotal Phase 2 trial in BCC.

Sanofi and Regeneron joint presentations at ESMO (Free ESMO Whitepaper) include:

Cemiplimab, a human PD-1 monoclonal antibody, in patients with recurrent or metastatic cervical cancer: Interim data from phase 1 cohorts
Danny Rischin Oct 20/12:30-13:30/958P

Cemiplimab, a human monoclonal anti-PD-1, plus radiotherapy in advanced non-small cell lung cancer (NSCLC): Results from a Phase 1 expansion cohort (EC 2)
Victor Moreno, Oct 20/12:30-13:30/1162P

Phase 1 study of cemiplimab, a human monoclonal anti-PD-1, in patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC): Longer follow-up efficacy and safety data
Taofeek K. Owonikoko, Oct 21/12:45-13:45/1292P

Cemiplimab, a human monoclonal anti-PD-1, in patients with advanced or metastatic hepatocellular carcinoma (HCC): Data from an expansion cohort in a Phase 1 study
Michael J. Pishvaian, Oct 20/12:30-13:30/1151P

Phase 1 expansion cohort results of cemiplimab, a human PD-1 monoclonal antibody, in combination with radiotherapy, cyclophosphamide and GM-CSF, in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC)
Hani Babiker, Oct 20/12:30-13:30/1171P

Phase 2 study of cemiplimab, a human monoclonal anti-PD-1, in patients with advanced basal cell carcinoma (BCC) who experienced progression of disease on, or were intolerant of prior hedgehog pathway inhibitor therapy
Karl D. Lewis, Oct 20/12:30-13:30/1240TiP

Libtayo is being developed jointly by Sanofi and Regeneron under a global collaboration agreement. The potential uses of Libtayo as a treatment for NSCLC, cervical cancer, BCC, HCC and HNSCC are investigational, and its safety and efficacy have not been evaluated by any regulatory authority for these cancers.

Libtayo is currently approved in the U.S. for the treatment of patients with metastatic CSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation. The generic name for Libtayo in the U.S. is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the US Food and Drug Administration. Sanofi Genzyme, the specialty care global business unit of Sanofi, and Regeneron market Libtayo jointly in the U.S. The safety and efficacy of Libtayo have not been evaluated by any regulatory authority outside of the U.S. for the treatment of advanced CSCC.

IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS

What is the most important information I should know about Libtayo?

Libtayo is a medicine that may treat a type of skin cancer by working with your immune system. Libtayo can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your healthcare provider right away if you develop any symptoms of the following problems or these symptoms get worse:

Lung problems (pneumonitis). Signs and symptoms of pneumonitis may include new or worsening cough, shortness of breath, and chest pain.
Intestinal problems (colitis) that can lead to tears or holes in your intestine. Signs and symptoms of colitis may include diarrhea (loose stools) or more frequent bowel movements than usual; stools that are black, tarry, sticky or that have blood or mucus; and severe stomach-area (abdomen) pain or tenderness.
Liver problems (hepatitis). Signs and symptoms of hepatitis may include yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, and feeling less hungry than usual.
Hormone gland problems (especially the adrenal glands, pituitary, thyroid and pancreas). Signs and symptoms that your hormone glands are not working properly may include headaches that will not go away or unusual headaches, rapid heartbeat, increased sweating, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, feeling cold, constipation, deeper voice, very low blood pressure, urinating more often than usual, nausea or vomiting, stomach-area (abdomen) pain, and changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness.
Kidney problems, including nephritis and kidney failure. Signs of these problems may include decrease in your amount of urine, blood in your urine, swelling in your ankles, and loss of appetite.
Skin problems. Signs of these problems may include rash, itching, skin blistering, and painful sores or ulcers in the mouth, nose, throat, or genital area.
Problems in other organs. Signs of these problems may include headache, tiredness or weakness, sleepiness, changes in heartbeat (such as beating fast, seeming to skip a beat, or a pounding sensation), confusion, fever, muscle weakness, balance problems, nausea, vomiting, stiff neck, memory problems, seizures (encephalitis), swollen lymph nodes, rash or tender lumps on skin, cough, shortness of breath, vision changes, or eye pain (sarcoidosis), seeing or hearing things that are not there (hallucinations), severe muscle weakness, low red blood cells (anemia), bruises on the skin or bleeding, and changes in eyesight.
Rejection of a transplanted organ. Your doctor should tell you what signs and symptoms you should report and monitor you, depending on the type of organ transplant that you have had.
Infusion (IV) reactions that can sometimes be severe and life-threatening. Signs of these problems may include chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, fever, feeling of passing out, back or neck pain, and facial swelling.

Getting medical treatment right away may help keep these problems from becoming more serious.

Your healthcare provider will check you for these problems during your treatment with Libtayo. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may delay or completely stop treatment if you have severe side effects.

Before you receive Libtayo, tell your healthcare provider about all your medical conditions, including if you:

have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus;
have had an organ transplant;
have lung or breathing problems;
have liver or kidney problems;
have diabetes;
are pregnant or plan to become pregnant; Libtayo can harm your unborn baby

Females who are able to become pregnant:

Your healthcare provider will give you a pregnancy test before you start treatment.
You should use an effective method of birth control during your treatment and for at least 4 months after your last dose of Libtayo. Talk with your healthcare provider about birth control methods that you can use during this time.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Libtayo.
are breastfeeding or plan to breastfeed. It is not known if Libtayo passes into your breast milk. Do not breastfeed during treatment and for at least 4 months after the last dose of Libtayo.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Libtayo include tiredness, rash, and diarrhea. These are not all the possible side effects of Libtayo. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Regeneron Pharmaceuticals and Sanofi at 1-877-542-8296.

Please see accompanying full Prescribing Information, including Medication Guide.

What is Libtayo?

Libtayo is a prescription medicine used to treat people with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC) that has spread or cannot be cured by surgery or radiation.