On March 17, 2020 OncoSec Medical Incorporated (NASDAQ:ONCS) (the "Company" or "OncoSec"), a company developing late-stage intratumoral cancer immunotherapies, reported the publication of positive TAVO monotherapy data in patients with metastatic melanoma in the Annals of Oncology (Press release, OncoSec Medical, MAR 17, 2020, View Source [SID1234555651]). The publication titled, "Intratumoral Delivery of Tavokinogene Telseplasmid Yields Systemic Immune Responses in Metastatic Melanoma Patients," features data previously highlighted at both American Association of Cancer Research (AACR) (Free AACR Whitepaper) and the Melanoma Bridge annual meetings. Annals of Oncology is the official publication of the European Society for Medical Oncology.

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The complete publication in Annals of Oncology is linked here and available on OncoSec’s website at View Source

The publication describes OncoSec’s study of patients with Stage III/IV melanoma who were treated intratumorally with plasmid encoding IL-12 (tavokinogene telseplasmid or TAVO), followed by electroporation on days 1, 5, and 8 every 90 days in the main study with additional patients treated in two exploration cohorts with alternative schedules. Correlative analyses for programmed death-ligand 1 (PD-L1), flow cytometry to assess changes in immune cell subsets and analysis of intratumoral immune-related gene expression were carried out on pre-and post-treatment samples from study patients, as well as from additional patients treated during exploration of additional dosing schedules beyond the pre-specified protocol dosing schedule. Response was measured by study-specific criteria to maximize detection of latent and potentially transient immune responses in patients with multiple skin lesions. Toxicities were graded by the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).

The objective overall response rate (ORR) was 35.7% in the main study, with a complete response (CR) rate of 17.9%. The median progression-free survival in the main study was 3.7 months while the median overall survival was not reached at a median follow up of 29.7 months. A total of 46% of patients in all cohorts having both injected and uninjected lesions experienced regression of at least one of these uninjected lesions and 25% had a net regression of all untreated lesions. Transient procedural pain (n = 24, 80%) and injection site reactions were the most commonly experienced adverse events.

Transcriptomic and immunohistochemistry analysis showed that immune activation and co-stimulatory transcripts were up-regulated, with an increase of adaptive immune resistance.

The publication concluded that intratumoral TAVO was well-tolerated and led to systemic immune responses in advanced melanoma patients. While tumor regression and increased immune infiltration were observed in treated as well as untreated/distal lesions, adaptive immune resistance limited the response.

"TAVO treatment appears to drive a change in the immune microenvironment, which results in an immune response to melanoma with minimal systemic toxicity. These data demonstrate that this in situ tumor vaccination strategy may be a safe and effective approach to inducing multiple sustained, productive changes in the immune microenvironment that would be too toxic using similar systemic agents and drive significant clinical results," concluded study co-author Adil Daud, M.D., Department of Medicine, University of California, San Francisco. "We look forward to continued evaluation of the TAVO approach as a monotherapy in future clinical trials."

TAVO is currently being evaluated as a combination therapy in multiple clinical trials, including KEYNOTE-695, a pivotal trial in late-stage anti-PD-1 checkpoint refractory metastatic melanoma, and two phase 2 trials, one for triple negative breast cancer (TNBC) and a second for head and neck cancer. TAVO enables the intratumoral delivery of DNA-based IL-12, a naturally occurring protein with immune-stimulating functions. OncoSec’s technology, which employs electroporation, is designed to produce a controlled, localized expression of IL-12 in the tumor microenvironment, enabling the immune system to target and attack tumors throughout the body. Results from recently completed clinical studies of TAVO have demonstrated a local immune response, and subsequently, a systemic effect as either a monotherapy or combination treatment approach.

"While our ongoing pivotal KEYNOTE-695 study is evaluating TAVO and KEYTRUDA combination therapy in late-stage checkpoint refractory metastatic melanoma patients and has begun to yield positive results, publication of monotherapy data with TAVO demonstrates its utility as a standalone treatment in this patient population," stated Christopher Twitty, Ph.D., OncoSec’s Chief Science Officer and a co-author of the publication. "The increase in adaptive resistance observed in the tumor microenvironment, in particular PD-L1, makes TAVO a particularly well-suited partner with anti-PD-1 checkpoint therapies. We are encouraged to see such a high response rate and will continue to evaluate TAVO’s utility as a monotherapy for metastatic melanoma."

Annals of Oncology is the latest among a presently growing volume of peer-reviewed journals to highlight the potential of TAVO as a novel immunotherapy. A recent publication in Cancer Immunology Research, linked here, also explored the mechanism of activation of systemic immunity in patients from the TAVO monotherapy study in metastatic melanoma patients. Additionally, Clinical Cancer Research featured TAVO monotherapy data in Merkel cell carcinoma on the cover of its February 2020 issue, linked here. You can find a list of all TAVO publications and scientific presentations at View Source

On March 17, 2020 DiaMedica Therapeutics Inc. (Nasdaq: DMAC) reported that its fourth quarter 2019 financial results will be released after the markets close on Monday, March 23rd (Press release, DiaMedica, MAR 17, 2020, View Source [SID1234555650]). DiaMedica will host a live conference call on Tuesday, March 24th at 7:00 AM Central Time to discuss its business update and financial results.

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Conference Call details:

Date:

Tuesday, March 24, 2020

Time:

7:00 AM CT / 8:00 AM ET

Web access:

View Source

Dial In:

(844) 557-8483 (domestic)

(825) 312-2381 (international)

Conference ID:

9270458

Interested parties may access the conference call by dialing in or listening to the simultaneous webcast. Listeners should log on to the website or dial in 15 minutes prior to the call. The webcast will remain available for play back on our website, under investor events and presentations, following the earnings call and for 12 months thereafter. A telephonic replay of the conference call will be available until March 31, 2020, by dialing (800) 585-8367 (US Toll Free), (416) 621-4642 (International), replay passcode 9270458.

On March 17, 2020 Provectus (OTCQB: PVCT) reported that data from ongoing research into investigational lysosomal-targeting cancer immunotherapy PV-10 (rose bengal disodium) for the treatment of solid tumor and blood cancers had been accepted for presentation at the now terminated AACR (Free AACR Whitepaper) Annual Meeting 2020, which was originally scheduled to be held April 24-29 in San Diego, California (Press release, Provectus Biopharmaceuticals, MAR 17, 2020, View Source [SID1234555649]). Intratumoral injection with PV-10 yields immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells.1-4

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The details of the previously accepted abstract were:

Title: Association of heat shock proteins as chaperone for STING: A potential link in a key immune activation mechanism revealed by the novel anti-cancer agent PV-10
Abstract Control Number: 8165
Session Category: Clinical Research
Session Title: Inflammation, Immunity, and Cancer/Modifiers of the Tumor Microenvironment 1
Poster Board Number: 6
Permanent Abstract Number: 5393
This work was led by Aru Narendran, MD, PhD and his team of researchers at the Pediatric Oncology Experimental Therapeutics Investigators’ Consortium (POETIC) Laboratory for Pre-Clinical and Drug Discovery Studies at the University of Calgary (Canada).

On March 10th, according to AACR (Free AACR Whitepaper)’s board of directors, the AACR (Free AACR Whitepaper) Annual Meeting 2020 was terminated based on their evaluation of currently available information related to the novel coronavirus (COVID-19) outbreak and a rescheduled meeting is being planned for later this year.

About PV-10

PV-10 is undergoing clinical study for adult solid tumor cancers, like melanoma and cancers of the liver (including metastatic neuroendocrine tumors and metastatic uveal melanoma). PV-10 is also undergoing preclinical study for pediatric solid tumor cancers (like neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma) and pediatric blood cancers (like leukemia).5,6

Tumor Cell Lysosomes as the Seminal Drug Target

Lysosomes are the central organelles for intracellular degradation of biological materials, and nearly all types of eukaryotic cells have them. Discovered by Christian de Duve, MD in 1955, lysosomes are linked to several biological processes, including cell death and immune response. In 1959, de Duve described them as ‘suicide bags’ because their rupture causes cell death and tissue autolysis. He was awarded the Nobel Prize in 1974 for discovering and characterizing lysosomes, which are also linked to each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Building on the Discovery, Exploration, and Characterization of Lysosomes

Cancer cells, particularly advanced cancer cells, are very dependent on effective lysosomal functioning.7 Cancer progression and metastasis are associated with lysosomal compartment changes8,9, which are closely correlated with (among other things) invasive growth, angiogenesis, and drug resistance10.

PV-10 selectively accumulates in the lysosomes of cancer cells upon contact, disrupts them, and causes them to die. The physicochemical properties of lysosomes trap PV-10. A lumenal pH of 4.5 to 5.0 is ideal for the conversion of the hydrophilic RB salt into the hydrophobic (lipophilic) lactone version. Provectus1,11, external collaborators5, and other researchers12-14 have independently shown that PV-10 (RB) triggers each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Cancer Cell Autolytic Death via PV-10: PV-10 inducing autolytic cell death, or death by self-digestion, in Hepa1-6 murine HCC cells can be viewed in this Provectus video of the event (ethidium homodimer [ED-1] stains DNA, but is excluded from intact nuclei; lysosensor green [LSG] stains intact lysosomes; the video is provided in 30-second frames; the event has a duration of approximately one hour). Exposure to PV-10 triggers the disruption of lysosomes, followed by nucleus failure and autolytic cell death. Identical responses have been shown by the Company in HTB-133 human breast carcinoma (which can be viewed in this Provectus video; this event has a duration of approximately two hours) and H69Ar human multidrug-resistant small cell lung carcinoma. Cancer cell autolytic cell death was reproduced by research collaborators from POETIC using relapsed and refractory human pediatric neuroblastoma cells to show that lysosomes are disrupted upon exposure to PV-10.5

Immune Signaling Pathways: PV-10 causes acute oncolytic destruction of injected tumors (i.e., cell death), mediating several identified immune signaling pathways studied to date, such as the release of danger-associated molecular pattern molecules (DAMPs) and tumor antigens that initiate an immunologic cascade where local response by the innate immune system facilitates systemic anti-tumor immunity by the adaptive immune system. The DAMP release-mediated adaptive immune response activates lymphocytes, including CD8+ T cells, CD4+ T cells, and NKT cells, based on clinical and preclinical experience in multiple tumor types. Other mediated immune signaling pathways that have been identified include poly-ADP ribose polymerase (PARP) cleavage and, now, stimulator of interferon genes (STING), which plays an important role in innate immunity. PV-10 is the first cancer drug that may facilitate multiple, complementary, immune system signaling pathways.15

Orphan Drug Designations (ODDs)

ODD status has been granted to PV-10 by the U.S. Food and Drug Administration for the treatments of metastatic melanoma in 2006, hepatocellular carcinoma in 2011, neuroblastoma in 2018, and ocular melanoma (including uveal melanoma) in 2019.

Drug Product

Rose bengal disodium (RB) (4,5,6,7-tetrachloro-2’,4’,5’,7’-tetraiodofluorescein disodium salt) is a small molecule halogenated xanthene and PV-10’s active pharmaceutical ingredient. PV-10 drug product is a formulation of 10% w/v RB in 0.9% saline, supplied in single-use glass vials containing 5 mL (to deliver) of solution, and administered without dilution to solid tumors via intratumoral injection.

Intellectual Property (IP)

Provectus’ IP includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the process by which pharmaceutical grade RB and related xanthenes are produced, reducing the formation of previously unknown transhalogenated impurities that exist in commercial grade RB in uncontrolled amounts. The requirement to control these impurities is in accordance with International Conference on Harmonisation (ICH) guidelines for the manufacturing of an injectable pharmaceutical. US patent numbers are 8,530,675, 9,273,022, and 9,422,260, with expirations ranging from 2030 to 2031.

The Company’s IP also includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the combination of PV-10 and systemic immunomodulatory therapy (e.g., anti-CTLA-4, anti-PD-1, and anti-PD-L1 agents) for the treatment of a range of solid tumor cancers. US patent numbers are 9,107,887, 9,808,524, 9,839,688, and 10,471,144, with expirations ranging from 2032 to 2035.

On March 17, 2020 BioSpecifics Technologies Corp. (NASDAQ: BSTC), a biopharmaceutical company that originated and continues to develop collagenase-based therapies with a first in class collagenase-based product marketed as XIAFLEX in North America, reported its financial results for the fourth quarter and full year ended December 31, 2019 and provided a corporate update (Press release, BioSpecifics Technologies, MAR 17, 2020, View Source [SID1234555648]).

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"BioSpecifics generated strong growth in 2019. We reported a 16% increase in royalty revenue received from our partner Endo’s sales of XIAFLEX and our fully diluted earnings per share grew by 22%. Looking forward, we have a number of reasons to be enthusiastic about the future growth potential for XIAFLEX. First, the market for XIAFLEX in Dupuytren’s contracture and Peyronie’s disease continues to expand, second the FDA’s decision on Endo’s new BLA for the treatment of cellulite is expected in July 2020 and third Endo has announced the commencement of development programs in two new indications, adhesive capsulitis and plantar fibromatosis," said J. Kevin Buchi, chief executive officer of BioSpecifics. "Operating from a position of sound financial strength, we intend to explore opportunities beyond XIAFLEX."

Fourth Quarter and Full Year 2019 Financial Results

BioSpecifics reported net income of $7.3 million for the fourth quarter ended December 31, 2019, or $1.00 per basic share and $1.00 per share on a fully diluted basis, compared to net income of $6.2 million, or $0.85 per basic share and $0.84 per share on a fully diluted basis, for the same period in 2018. For the full year ended December 31, 2019, the Company reported a net income of $24.5 million, or $3.34 per basic share and $3.33 per share on a fully diluted basis, compared to a net income of $20.1 million, or $2.77 per basic share and $2.73 per share on a fully diluted basis for the same period in 2018.

Total revenue for the fourth quarter ended December 31, 2019 was $11.8 million, compared to $9.9 million for the same period in 2018. For the full year ended December 31, 2019, total revenue was $38.2 million, compared to $33.0 million for the same period in 2018.

As of December 31, 2019, BioSpecifics had cash and cash equivalents and investments of $105.8 million, compared to $82.0 million as of December 31, 2018.

As of December 31, 2019, BioSpecifics had 7,339,578 million shares of common stock outstanding.

Commercial & Pipeline Highlights and Anticipated Upcoming Milestones

BioSpecifics’ Royalty Revenues from the XIAFLEX Commercial Franchise Grew by 16% Year-Over-Year for 2019: XIAFLEX royalty revenue growth was attributable to royalties associated with higher net sales of XIAFLEX by Endo International plc (Endo), in Dupuytren’s contracture and Peyronie’s disease.
Net Sales of XIAFLEX Expected to Continue to Grow in 2020: BioSpecifics’ partner, Endo, expects that XIAFLEX full year revenue growth will be approximately 20 percent in 2020.
Endo’s Biologics License Application (BLA) filing for CCH for Treatment of Cellulite Accepted by U.S. Food and Drug Administration (FDA) in November 2019: On November 19, 2019, the FDA accepted for review the original BLA for CCH for the treatment of cellulite in the buttocks. The Prescription Drug User Fee Act (PDUFA) date for the BLA, has been set for July 6, 2020.
Development in Two New Indications, Adhesive Capsulitis and Plantar Fibromatosis, Announced in 2020: Endo announced in 2020 that it expects to begin development in two new indications, adhesive capsulitis and plantar fibromatosis. Adhesive capsulitis, also known as frozen shoulder, is an inflammation and thickening of the shoulder capsule due to collagen which causes decreased motion in the shoulder. Plantar fibromatosis is a non-malignant thickening of the feet’s deep connective tissue or fascia. There are currently no FDA-approved pharmaceutical therapies available to treat either condition.

On March 17, 2020 Varian (NYSE: VAR) reported, Proton International at UAB has now treated its first cancer patient with the Varian ProBeam Compact proton therapy system (Press release, Varian Medical Systems, MAR 17, 2020, View Source [SID1234555646]). The center, a collaboration between The University of Alabama at Birmingham (UAB) and Proton International, opened in January 2020 and is the first proton therapy center in Alabama and one of only 35 proton therapy centers in the United States.

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"We celebrate this first of many patients who will be treated at UAB with this advanced technology," said Will Ferniany, Ph.D., CEO of the UAB Health System. "The Varian ProBeam system is one of the most advanced tools available and our physicians are now able to improve care and precision of treatment for their cancer patients. With this technology, we will improve the quality of life for many cancer patients and their families in Alabama and the Southeast."

Dr. James Bonner, chairman of the UAB Radiation Oncology Department added, "This is a landmark moment for the patients of Alabama. After so many years of planning, we have been able to bring this technologically advanced treatment to the UAB Cancer Center."

Proton therapy is the most sophisticated radiotherapy technology available today. It uses protons, accelerated to about two-thirds the speed of light, or more than 100,000 miles per second, to destroy cancer cells, while minimizing exposure to nearby healthy tissues.

"We are pleased to have reached this important milestone for the patients of Alabama and the region," said Chris Chandler, CEO of Proton International. "Together with Varian and UAB, this public – private approach has resulted in the development of a unique service that otherwise may not have been available to patients. Varian’s commitment has resulted in enhanced care for patients."

"One of our primary goals at Varian is to improve cancer care for patients around the globe," said Kolleen Kennedy, president, Proton Solutions and chief growth officer at Varian. "Through our partnership with Proton International and UAB, cancer patients in Alabama now have access to the most advanced, efficient and effective treatment, closer to home."

The Varian ProBeam Compact system is the only clinical single room system capable of fully rotational intensity modulated proton therapy (IMPT). Treatments can be delivered with an unmatched combination of speed, flexibility and cost efficiency. The full-featured ProBeam Compact includes a cyclotron, high-definition pencil beam scanning technology for IMPT, a fully rotational gantry, robotic patient positioning tools, and a comprehensive suite of motion management tools. It incorporates cone beam CT imaging for positioning the patient based on high quality anatomical images with excellent soft tissue resolution, and Varian’s world-class Eclipse and ARIA software systems for the planning and managing of treatments.