On December 16, 2019 Immune Therapeutics, Inc. (OTCQB: IMUN) ("Immune", "IMUN" or the "Company") and Aletheia Therapeutics Corp. ("Aletheia"), a privately held development-stage oncology therapeutics company, reported that Immune will acquire Aletheia in an all-stock transaction (Press release, Immune Therapeutics, DEC 16, 2019, View Source [SID1234552398]). Pursuant to completion of a definitive agreement, Immune will acquire all of the outstanding shares of Aletheia in exchange for Immune common stock . In connection with the acquisition, the Aletheia management team will join the leadership of the combined Company as well as selected Board members of Aletheia.

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Over the past several years researchers have demonstrated that cancer is inherently heterogenous and a single tumor can have up to one hundred different cell phenotypes. This knowledge has led to a new approach in cancer therapy in that targeting several different biological targets in cancer provides for better efficacy and lower toxicity. Specifically, a combination of drugs that each target an independent critical pathway in cancer growth is becoming widely recognized as the future of cancer treatment. The combined company will be focused on developing and commercializing precision cancer therapies by simultaneously targeting two or more of the following biological targets depending on the make-up of a patients’ cancer: DNA repair, T-cell activation, metabolic dysfunction, angiogenesis, apoptosis or inflammation.

"With this acquisition we will be able to develop a diverse platform of therapies that target multiple critical biological pathways that will be designed for an individual’s cancer," said Michael Handley, chief executive officer and president, Immune Therapeutics. "The combination of Aletheia’s diverse oncology product pipeline with Immune’s Lodonal and MENK product candidates will create an industry leading oncology company."

"Following an extensive evaluation and diligence process, the Immune Board of Directors concluded that the acquisition of Aletheia, with a strong platform technology, seasoned leadership team, and compelling clinical development plan, offered an excellent opportunity to create shareholder value for Immune," stated Dr. Roscoe Moore, the chairman of Immunes Board of Directors. "We believe Aletheia represents an attractive acquisition target for Immune, offering a novel approach to creating precision therapies for cancer patients with unmet medical needs."

Under the initial terms announced today, Immune, through a subsidiary, will initiate an offer to acquire all outstanding shares of Aletheia. The closing of the offer will be subject to certain conditions, including completing due diligence, the employment of the Aletheia management team to Immune management team and the assignment of all intellectual property to Immune. Furthermore, Aletheia has signed definitive stock purchase agreement with an investor group for $25 million that should fund before the end of the year. Once the acquisition is complete Aletheia and Immune will be funded with sufficient capital to execute on the product development strategy in 2020. The acquisition is expected to close early in the first quarter of 2020.

On December 16, 2019 GlaxoSmithKline reported treatment with the investigational single-agent belantamab mafodotin resulted in a clinically meaningful 31% overall response rate (ORR) with the 2.5 mg/kg regimen in patients with heavily pre-treated multiple myeloma (Press release, GlaxoSmithKline, DEC 16, 2019, View Source [SID1234552397]). Patients in the trial received a median of seven prior lines of treatment, were refractory to an immunomodulatory drug and a proteasome inhibitor and were refractory and/or intolerant to an anti-CD38 antibody. The median duration of response has not been reached at six months of follow-up.

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Full results from the DREAMM-2 (DRiving Excellence in Approaches to Multiple Myeloma) study of belantamab mafodotin were published today in The Lancet Oncology. GSK also confirmed submission of a Biologics License Application to the US Food and Drug Administration (FDA) seeking approval of belantamab mafodotin for the treatment of patients with relapsed or refractory multiple myeloma whose prior therapy included an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody. Belantamab mafodotin is not currently approved for use anywhere in the world.

Dr Hal Barron, Chief Scientific Officer and President R&D, GSK said: "Patients with multiple myeloma whose disease has progressed despite currently available therapy have limited options and poor outcomes. Data from the DREAMM-2 study show that, if approved, belantamab mafodotin could offer an important new treatment option for these patients."

DREAMM-2 is an open label study of belantamab mafodotin, a humanised, immunoconjugate against B-cell maturation antigen (BCMA).[i] Patients in the trial had actively progressing multiple myeloma that had worsened despite current standard of care and were randomised to two arms to receive either 2.5 mg/kg or 3.4 mg/kg belantamab mafodotin every three weeks. Overall, patients in DREAMM-2 had more advanced disease, poorer prognosis and performance status and also had a greater number of prior lines of therapy in comparison with patients in DREAMM-1, the first time in human study of belantamab mafodotin.

Dr Sagar Lonial, MD, Chief Medical Officer, Winship Cancer Institute of Emory University, Chair of Emory Department of Hematology and Medical Oncology and Principal Investigator for DREAMM-2, said: "Each day in my practice, I see patients who would benefit from additional therapeutic options because their disease has advanced and is no longer responding to available treatments. In recent years, BCMA has become one of the most promising targets in multiple myeloma research. The data published today from DREAMM-2 not only reinforce the significance of BCMA as a potentially viable target, but also underscore the potential of belantamab mafodotin, if approved, as a practical treatment option in this patient population."

The results demonstrated in DREAMM-2 were consistent with those observed in a similar subset of patients in the DREAMM-1 study. Based on these data, GSK is moving forward with a US FDA submission seeking approval of the 2.5 mg/kg dose. If approved, belantamab mafodotin will be the first anti-BCMA agent available in the US.

Thirty of the 97 patients (31%) in the 2.5 mg/kg cohort achieved an overall response. Of these responders, 18 patients achieved a very good partial response or better, including three patients with stringent complete or complete responses. In addition, overall survival in patients achieving a response was not reached in the six month follow-up period.

The safety and tolerability profile was consistent with previously reported data on belantamab mafodotin. The three most commonly reported Grade 3 or 4 adverse events in the 2.5 mg/kg arm were keratopathy (27%), thrombocytopenia (20%) and anaemia (20%). Keratopathy is characterized as changes in the corneal epithelium as seen on eye examination which can manifest with or without symptoms. Corneal events leading to treatment discontinuation affected 1% of patients in the 2.5 mg/kg cohort.

Additional studies are testing the effect of belantamab mafodotin as third-line monotherapy in relapsed/refractory multiple myeloma and in combination with standard and novel treatments in the first and second line setting as part of the broader DREAMM clinical development programme.

In 2017, GSK2857916 was granted Breakthrough Therapy designation from the US FDA and PRIME designation from the European Medicines Agency.

In the US, an expanded access program for belantamab mafodotin is available to eligible patients with multiple myeloma. For patients to be considered for enrollment in the programme, they must be assessed according to specific inclusion and exclusion criteria by their treating physician. Additional information about the expanded access protocol can be found on ClinicalTrials.gov (NCT03763370).

About multiple myeloma
Multiple myeloma is the second most common blood cancer and is generally considered treatable, but not curable.[ii] Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.[iii]

About B-cell maturation antigen (BCMA)
The normal function of BCMA is to promote plasma cell survival by transduction of signals from two known ligands, BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand). This pathway has been shown to be important for myeloma cell growth and survival. BCMA expression is limited to B cells at later stages of development. BCMA is expressed at varying levels in myeloma patients and BCMA membrane expression is universally detected in myeloma cell lines.[iv]

About the DREAMM clinical trial programme for belantamab mafodotin (GSK2857916)
Belantamab mafodotin is an investigational immunoconjugate comprising a humanised anti-B cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent auristatin F via non-cleavable linker. The drug linker technology is licensed from Seattle Genetics; monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa.

Trial Name

GSK ID/NCT ID

Status

Design

DREAMM-1

117159/ NCT02064387

Completed

A Phase I Open-label Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of Belantamab Mafodotin (GSK2857916) in Subjects with Relapsed/Refractory Multiple Myeloma and Other Advanced Hematologic Malignancies Expressing BCMA

DREAMM-2

205678/ NCT03525678

Active, not recruiting

A Phase II Study to Investigate the Efficacy and Safety of Two Doses of Belantamab Mafodotin (GSK2857916) in Subjects with Relapsed/Refractory Multiple Myeloma Who are Refractory to a Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed Prior Treatment with an Anti-CD38 Antibody

DREAMM-3

207495

Planned

A Phase III Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin (GSK2857916) Compared to Pomalidomide plus low-dose Dexamethasone (Pom/Dex) in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-4

205207/ NCT03848845

Recruiting

A Phase I/II Single Arm Open-Label Study to Explore Safety and Clinical Activity of Belantamab Mafodotin (GSK2857916) Administered in Combination with Pembrolizumab in Subjects with Relapsed/Refractory Multiple Myeloma

DREAMM-5

208887/

NCT04126200

Recruiting

A Phase I/II, Randomized, Open-label Platform Study of Belantamab Mafodotin (GSK2857916) with Innovative Combination Anti-Cancer Treatments in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-6

207497/ NCT03544281

Recruiting

A Phase I/II Randomized Study to Evaluate Safety, Tolerability and Clinical Activity of Belantamab Mafodotin (GSK2857916) Administered in Combination with Lenalidomide plus Dexamethasone (Arm A), or in Combination with Bortezomib plus Dexamethasone (Arm B) in Subjects with Relapsed/Refractory Multiple Myeloma

DREAMM-7

207503

Planned

A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Bortezomib plus Dexamethasone versus Daratumumab, Bortezomib, and Dexamethasone in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-8

207499

Planned

A Phase III, Multicentre, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin (GSK2857916) in Combination with Pomalidomide plus Low-Dose Dexamethasone (BPd) versus Pomalidomide plus Bortezomib and Low-Dose Dexamethasone (PVd) in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-9

209664/ NCT04091126

Planned

A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Bortezomib plus Lenalidomide and Low-Dose Dexamethasone (VRd) vs. VRd in Participants with Newly Diagnosed Multiple Myeloma who are Ineligible for Transplant

DREAMM-10

207500

Planned

A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with a Novel Agent versus SoC

ISS / GSK Co-Sponsored Study

209418/ NCT03715478

Recruiting

A Phase I/II Dose-escalation and Dose-expansion Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Pomalidomide plus Low-dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma Who Have Received Two or More Prior Lines of Therapy That Must Have Included Lenalidomide and a Proteasome Inhibitor

GSK in Oncology
GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics, and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

On December 16, 2019 The board of directors of Eli Lilly and Company (NYSE: LLY) reported a 15 percent increase in its quarterly dividend (Press release, Eli Lilly, DEC 16, 2019, View Source [SID1234552396]). The dividend for the first quarter of 2020 will be $0.74 per share on outstanding common stock. This raises the annual indicated rate to $2.96 per share.

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The dividend is payable March 10, 2020, to shareholders of record as of the close of business on February 14, 2020.

On December 16, 2019 Dynavax Technologies Corporation (NASDAQ: DVAX), a biopharmaceutical company focused on developing and commercializing novel vaccines, reported that Ryan Spencer has been appointed Chief Executive Officer and to the Board of Directors (Press release, Dynavax Technologies, DEC 16, 2019, View Source [SID1234552395]). David Novack has been appointed President and Chief Operating Officer, reporting to Mr. Spencer. These appointments are effective December 16, 2019.

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"Through a rigorous, comprehensive search process, Ryan emerged as the right business leader to guide Dynavax, given his strong command of our business and proven ability to lead and drive commercial execution in a complex operating environment," commented Arnold L. Oronsky, Ph.D., Chairman of the Board of Directors. "Ryan’s expertise across corporate strategy, finance, and commercialization, with a track record of leadership, combined with David’s tremendous experience in vaccine development and manufacturing, results in an executive leadership team with the full complement of experience required to drive the growth and success of Dynavax."

Mr. Spencer, who joined Dynavax in 2006, has held roles of increasing responsibility, building from a foundation in corporate finance to business strategy and investor relations, and culminating in his role as Senior Vice President, Commercial. Since May of 2019, Mr. Spencer has served as the Company’s interim co-President, a role he shared with Mr. Novack.

Mr. Novack joined Dynavax in 2013, and has led the company’s technical operations, supply chain, and quality teams through FDA approval, launch, and commercialization of HEPLISAV-B. Mr. Novack has more than 30 years of relevant industry experience, with more than 20 years of direct vaccine industry experience. Prior to Dynavax, Mr. Novack was at Novartis where he served in various roles, including Global Head of Technical Operations and Supply Chain for Diagnostics, and Global Head of Manufacturing Strategy for Vaccines.

"I am honored to take on this role at a transformational time for Dynavax as we continue to build on our commercial success with HEPLISAV-B," commented Ryan Spencer, Chief Executive Officer. "It is a privilege to work with a fantastic team and a product that, based on its proven clinical profile, has the potential to become the standard-of-care, adult hepatitis B vaccine in the U.S. Dynavax is well positioned to build a global vaccine business that improves patients’ lives, starting with HEPLISAV-B."

On December 16, 2019 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that Professor Dr. Richard P. Baum reported his initial independent clinical experience with FAP-2286 in named-patient use at the International Centers for Precision Oncology (ICPO) Foundation Symposium in Bad Berka, Germany (Press release, Clovis Oncology, DEC 16, 2019, View Source [SID1234552394]). At Prof. Dr. Baum’s clinic, FAP-2286 was linked to Gallium-68 as a tumor-imaging compound using PET/CT and to Lutetium-177 as a therapeutic agent.

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In the first named-patient experience with FAP-2286, Prof. Dr. Baum imaged 10 patients with advanced solid tumors, including breast, pancreatic, colorectal and ovarian cancers, with PET/CT using FAP-2286 linked to the commonly used imaging agent Gallium-68 for PET/CT imaging. In each case, Prof. Dr. Baum found that the FAP-PET/CT showed consistency with standard of care 18F-FDG-PET/CT scans for the same patients, including identification of both primary and metastatic lesions in liver, lung, bones, lymph nodes and other sites. Prof. Dr. Baum did not observe accumulation of FAP-2286 in healthy tissues of these 10 patients, except, as anticipated in the kidneys where FAP-2286 is excreted.

In addition, Prof. Dr. Baum treated 10 patients with FAP-2286 linked with Lutetium-177. Lutetium-177 is a radionuclide approved for use with somatostatin receptor targeting agents and is in development for use with other compounds. The initial single dose administration showed significant, specific accumulation in primary tumors and metastatic lesions. In this first-in-human experience, patients received a relatively low dose of Lutetium-177. Prof. Dr. Baum reported a lack of significant adverse effects within the first two months of follow-up and an absence of myelosuppression or damage to any other tissue, including the kidneys. Prof. Dr. Baum intends to administer a second dose of FAP-2286 linked with Lutetium-177 this month.

"I’m extremely pleased with our experience thus far with FAP-2286," said Prof. Dr. Baum, Chairman and Clinical Director, Theranostics Center for Radiomolecular Precision Oncology at Zentralklinik, Bad Berka, Germany. "As an imaging agent alone, it appears consistent with 18FDG-PET/CT scanning on a schedule that is much more convenient for patients. In addition, while obviously early, when linked to Lutetium-177, FAP-2286 was very well-tolerated, showed encouraging residence time in the tumor lesions, and appears to have, after only one low dose, provided symptomatic relief in several of the patients treated. I believe that FAP as a target and FAP-2286 as a drug candidate represent a very exciting new area of research in molecular targeted radiotherapy."

"While these examples from named-patient use do not represent a clinical study, we are pleased that the initial imaging and treatment experience with FAP-2286 are consistent with the preclinical data that led to our enthusiasm for FAP as a target and for FAP-2286 as a highly differentiated targeted radionuclide therapy," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We look forward to completing the pre-clinical work in order to file our IND for FAP-2286 in the second half of 2020 and to initiating formal clinical development for this very promising compound."

Physicians in Germany and certain other countries may treat patients suffering from a life-threatening disease or a disease leading to severe disability with experimental drugs if no other appropriate options are available under named-patient and similar programs. A physician may initiate treatment for specific patients until there is commercial product available and patients are encouraged to enroll in clinical trials where possible. Named-patient programs are not clinical trials and the treating physician is solely responsible for all decisions, including dose and assessment of efficacy and safety, and the drug sponsor has no role in decisions.

About FAP-2286

FAP-2286 is a preclinical candidate discovered by 3B Pharmaceuticals under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein alpha (FAP). FAP is highly expressed in cancers, including more than 90 percent of breast, lung, colorectal and pancreatic carcinomas. Clovis is planning to file an investigational new drug application (IND) for FAP-2286 in the second half of 2020. Clovis will conduct the global clinical trials and holds U.S. and global rights, excluding Europe.

FAP-2286 is an unlicensed medical product.

About Fibroblast Activation Protein Alpha (FAP)

Fibroblast activation protein alpha, or FAP, is highly expressed in cancer-associated fibroblasts (CAFs) which are found in the majority of cancer types, potentially making it a suitable target across a wide array of solid tumors. FAP is highly expressed in many epithelial cancers, including more than 90 percent of breast, lung, colorectal and pancreatic carcinomas.1 CAFs are highly prevalent in the tumor microenvironment of many cancers and persist through all malignant stages of a tumor, from primary tumor to metastasis. FAP has limited expression on normal fibroblasts, reducing the potential for effects in normal tissue.

About Peptide-Targeted Radionuclide Therapy (PTRT)

Peptide-targeted radionuclide therapy involves a small amount of radioactive material (radionuclide) that is combined with a cell-targeting moiety peptide for the treatment of cancer; PTRT is considered a form of radiopharmaceuticals. The targeting peptide is able to recognize and bind to specific features of tumors, such as antigens and cell receptors. When injected into the patient’s bloodstream, the peptide attaches to cancer cells or cancer-associated stromal cells, delivering a high dose of radiation to the tumor while sparing normal tissues.

About FAP-Targeted Radiopharmaceuticals

Clinical studies of small molecule imaging agents targeting FAP have validated this target in a diverse number of cancer indications and support the further evaluation of peptide-targeted radionuclide therapy. FAP-targeted radiopharmaceuticals have at least two potential modes of anti-tumor activity: radiation crossfire, in which tumor cells are irradiated due to their close proximity to CAFs; and depletion of CAFs, disrupting the communication between the tumor cells and the tumor stroma. In addition, in certain tumor types, such as sarcoma and mesothelioma, FAP is expressed on the tumor cells themselves, and in those tumors, FAP-targeted radiopharmaceuticals may have a direct effect.