On May 27, 2021 Aptevo Therapeutics Inc. ("Aptevo") (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIRTM and ADAPTIR-FLEXTM platform technologies reported that the company has initiated the expansion phase of lead anti-leukemia drug candidate, APVO436, in adult patients with acute myeloid leukemia (AML) with a multi-center, multi-arm trial using the active recommended dose identified in the dose escalation phase (Part 1) of the study (Press release, Aptevo Therapeutics, MAY 27, 2021, View Source [SID1234583271]). During Part 1, APVO436 exhibited a manageable side effect profile, encouraging single agent activity and a promising benefit to risk profile in relapsed AML patients. The Company has plans to submit data from the dose escalation phase for publication later this year.

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The dose expansion phase (Part 2), has been rationally designed to further evaluate the tolerability and clinical impact potential of APVO436 for indications of unmet and urgent medical need. During Part 2, the dose expansion phase of the study, a total of 90 AML patients will be enrolled into 5 cohorts of 18 patients each, as explained in the detailed and publicly available study information provided at CinicalTrials.gov (NCT03647800) The study will be conducted under an FDA-approved IND and has been Central IRB-approved. Patient enrollment is anticipated to commence in June. The goal of the expansion phase is to evaluate the safety and tolerability of APVO436 at the recommended Phase 2 dose level, when it is used as an adjunct to the standard of care and to obtain a preliminary assessment of the anti-leukemia activity of APVO436 containing experimental monotherapy and combination therapy modalities.

Protocol-specific training has started for the participating academic cancer centers in the US. Aptevo is planning to conduct Part 2 of the study at up to 20 clinical trial sites.

"The greatest challenge in AML is relapsed or refractory disease. For relapsed or refractory AML, there is no consensus on a single re-induction regimen" explained Dr. Fatih Uckun, leukemia expert and Chief Clinical Advisor. "By combining APVO436 with the standard of care, Aptevo hopes to develop an innovative approach that improves outcomes for patients with relapsed AML, who generally have a dismal prognosis," he stated.

Dr. Uckun explained further: "In addition, newly diagnosed AML patients with inherent drug resistance who have documented residual leukemia after standard frontline chemotherapy regimens, have a very poor prognosis and are in urgent need of therapeutic innovations. Part 2 of the Aptevo study will therefore seek proof of concept in the use of APVO436 as part of frontline multimodality regimens would enable the eradication of residual leukemia cells that have escaped standard chemotherapy. To this end we will carefully study the tolerability and clinical activity of APVO436 when used as rationally designed in each of the 5 cohorts of Part 2 of our Phase 1B study."

Overview of Cohorts

In Cohort 1, AML patients in relapse will be treated with the standard chemotherapy drug cytarabine or the standard chemotherapy triple drug combination MEC (mitoxantrone, etoposide, cytarabine) plus APVO436. Also treated in this cohort will be patients with primary refractory AML whose leukemia failed to respond to frontline standard induction chemotherapy.

In Cohort 2, AML patients in first relapse will receive a combination of APVO436 + venetoclax + azacitidine. Also included in this cohort will be newly diagnosed AML patients with a poor prognosis who will receive this novel combination as their frontline induction regimen.

In Cohort 3, AML patients with poor prognosis who are newly diagnosed will receive their frontline chemotherapy to induce a remission and APVO436 will be added if there is evidence of residual leukemia remaining. Also included in this cohort will be AML patients who experienced an early first relapse within 1 year of receiving their frontline chemotherapy. Such patients are generally known to have a dismal outcome.

In Cohort 4, AML patients in 1st remission who have evidence of residual leukemia, also known as minimal residual disease (MRD), will receive the standard drug oral azacytidine in combination with APVO436.

In Cohort 5, AML patients in 2nd remission who are MRD+ will be treated with APVO436 monotherapy.

"New treatments are urgently needed for frontline adverse risk and relapsed AML populations and I look forward to working with Dr. Uckun and other investigators for a step-wise evaluation of the clinical potential of APVO436", says Dr. Justin Watts, Associate Professor of Medicine at the University of Miami Sylvester Comprehensive Cancer Center.

"This week has been exciting for Aptevo, as we announced both positive results from the dose escalation part of our Phase 1 trial and the initiation of the expansion phase. We are particularly excited about the fact that APVO436 did not cause severe neutropenia in any of the AML patients treated so far. This is a potentially paradigm-shifting discovery as it provides the unique opportunity to integrate APVO436 into standard treatment regimens that inherently cause severe neutropenia," said Mr. Marvin White, President and CEO of Aptevo. "The initiation of Part 2 in our APVO436 study emphasizes our commitment to advance our ADAPTIR and ADAPTIR-FLEX platforms as integral parts of a novel standard of care for the most difficult-to-treat forms of cancer. We look forward to sharing interim data from Part 2 of the trial, later this year."

On May 27, 2021 Scientia Vascular may focus largely on producing medical devices of tiny proportions, reported that certainly doesn’t carry over to its latest wave of financing (Press release, Scientia Vascular, MAY 27, 2021, View Source [SID1234583261]).

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The Salt Lake City-based company, which develops not only a suite of microcatheters and guidewires but also the manufacturing technology it takes to produce them, has received $50 million in growth equity to support and expand that development.

The funding came solely from Vivo Capital, a global healthcare investment firm that has backed biotech and medtech companies through its multiple nine-figure venture funds, including, most recently, Esco Lifesciences’ $200 million series A.

The $50 million in growth capital will help speed up global sales and marketing efforts for Scientia’s existing products while also supporting new product development in the neurovascular stroke, peripheral vascular and interventional oncology markets.

RELATED: Surmodics gets FDA nod for Telemark microcatheter

Currently, Scientia’s product portfolio includes a handful of guidewires and microcatheters that, since their 2018 commercial launch, have been used primarily in neurovascular surgeries and specifically in stroke treatment.

Among these are the Plato line of microcatheters—including the Plato 17 model, which was cleared (PDF) by the FDA just last month—and the trio of Aristotle flexible guidewires. Additionally, last August, the company received FDA clearance for and began rolling out its Zoom Wire collection of guidewires, which are designed to lead catheters into the body during intensive, time-critical vascular operations, such as during ischemic or hemorrhagic stroke.

At the time of the Zoom Wire’s launch, John Lippert, Scientia’s founder and CEO, said in a statement that the company had plans to introduce an even wider line of guidewires and microcatheters under the Zoom umbrella in 2021.

Beyond designing and developing its range of neurovascular devices, Scientia also does all of its own manufacturing. To that end, the company has invented patented micromachining and microfabrication technologies to achieve high levels of stability and flexibility in its guidewires and catheters. Scientia has also automated much of this proprietary manufacturing process to ensure consistency in the quality of its products.

RELATED: FDA approves wireless brace that uses brainwaves to improve hand function in stroke patients

The realm of microcatheters and guidewires has long been dominated by medtech giants like Stryker and Boston Scientific, both of which boast a broad range of products for interventional vascular operations.

More recently, smaller startups have begun to challenge these behemoths with innovative takes on the products, whether through new manufacturing processes like Scientia’s or entirely new technology. In the latter category are companies like Sensome, which is developing sensor-equipped guidewires that use machine learning algorithms to analyze the tissue they come in contact with during stroke treatment.

On May 27, 2021 Vectura Group, a British pharmaceutical company focused on inhaled medicines, reported had agreed a 958 million pound ($1.36 billion) takeover by global investment firm The Carlyle Group (Press release, Carlyle Group, MAY 27, 2021, View Source [SID1234583254]).

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Shareholders will receive 136 pence in cash plus a dividend of 19 pence for each share under the terms of the offer, representing a 32% premium on the ex-dividend closing price of the stock on Tuesday, Vectura said.

Vectura’s Chairman Bruno Angelici said the company had made strong progress since embarking on a strategy in 2019 to become a leading inhalation-focused CDMO, or contract development and manufacturing organisation.

He said that while the board remained confident in the fundamentals of the group and its strategy, the "attractive offer" secured future value for shareholders in cash today.

Vectura has 13 key inhaled and 11 non-inhaled products marketed by partners with global royalty streams, and a diverse partnered portfolio of drugs in clinical development.

Its partners include Novartis, GSK, Bayer, Chiesi, Almirall, and Tianjin KingYork.

On May 27, 2021 Oncorus, Inc. (Nasdaq: ONCR), a viral immunotherapies company focused on driving innovation to transform outcomes for cancer patients, reported the nomination of its first Synthetic viral RNA (vRNA) immunotherapy clinical candidates, ONCR-021 and ONCR-788 (Press release, Oncorus, MAY 27, 2021, View Source [SID1234583253]). Oncorus’ pioneering intravenous (IV)-administered approach involves encapsulating the genomes of RNA viruses known to kill cancer cells (i.e., oncolytic viruses, or OVs) in a lipid nanoparticle (or LNP), creating a Synthetic vRNA immunotherapy. ONCR-021 encodes an optimized strain of Coxsackievirus A21 (CVA21), and ONCR-788 encodes for a modified version of the Seneca Valley Virus (SVV). Both CVA21 and SVV have extensive clinical experience and favorable safety profiles when administered IV. Oncorus’ novel Synthetic vRNA approach holds the potential for IV-administration and avoids the challenge of neutralizing antibodies seen in previous approaches with IV-administered OVs. Oncorus plans to investigate its novel Synthetic vRNA immunotherapies in multiple histologies including cancers of the lung both as monotherapy and in combination with immune checkpoint inhibitors and other cancer treatments.

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"There has been a notable rise in the development and approval of RNA-based vaccines, most prominently for COVID-19, and therapeutics for certain rare diseases. To date, however, there are no approved RNA-based cancer therapies. Simultaneously, the therapeutic benefit of viral immunotherapy

has been limited to intratumoral (iTu) administration, restricting broader applications of this modality. In addition, past investigational programs that utilized IV-administered natural OVs faced the challenge of neutralizing antibodies which likely hinders the clinical efficacy of later doses. Our proprietary Synthetic vRNA Immunotherapy Platform involves a highly innovative, novel combination of RNA- and OV-based modalities and, in doing so, holds the potential to create a new pillar in cancer therapy," said Theodore (Ted) Ashburn, M.D., Ph.D., President and CEO of Oncorus.

LNP-encapsulated IV-administered vRNA to create a "living immunostimulatory drug"

Developing IV-administered RNA medicines for cancer requires addressing two primary technological hurdles: first, getting adequate concentrations of the RNA-based drug candidate to all tumor cells, and second, limiting exposure to normal tissue throughout the body.

OVs, through rapid, self-amplification of their genomes in permissive cells and their ability to infect nearby cancer cells, are a potential answer to the challenge of the suboptimal LNP delivery of cargo RNA to tumor cells. In addition, OVs are selected or engineered to replicate more robustly in cells with deficiencies in antiviral responses, as is the case for cancer cells. OVs’ selectivity for tumors ensures that their genomes, when delivered by LNP, are minimally or not at all replicating in healthy tissues, thus potentially providing a large therapeutic window for Oncorus’ Synthetic vRNA immunotherapy candidates. Furthermore, the immunogenic cell death triggered by OVs, and the release of tumor antigens in an inflamed tumor microenvironment, are expected to broadly stimulate the immune system in its fight against cancer.

"Taken together, the oncolytic and immunogenic properties of OVs, combined with the broad tissue distribution enabled by IV-administered LNPs and the tumor selective self-amplification afforded by vRNA, opens the door to the successful application of IV-administered RNA medicines in cancer," explained Dr. Ashburn. "This approach holds the promise of improving outcomes for patients across multiple types of cancer, in particular those with cancers of the lung."

Christophe Quéva, Ph.D., Oncorus’ Chief Scientific Officer, said, "We are proud of our team’s work to advance both our oncolytic Herpes Simplex Virus and Synthetic Viral RNA Immunotherapy Platforms. With this dual-platform strategy, we are building a versatile pipeline of iTu-administered and IV-administered viral immunotherapy product candidates that will potentially enable the treatment of a broad range of cancer settings. We continue to advance our lead oHSV candidate, ONCR-177, through Phase 1 study, and we are working diligently to progress our lead synthetic candidates, ONCR-021 and ONCR-788, into the clinic."

ONCR-021 and ONCR-788 Clinical Development and In-House GMP Manufacturing

Oncorus plans to file an investigational new drug (IND) application for ONCR-021 in the first half of 2023 to enable clinical development for non-small cell lung cancer and other cancers such as hepatocellular carcinoma, clear cell renal cell carcinoma and melanoma, both as a single agent and in combination with immune checkpoint inhibitors. Following the IND filing for ONCR-021, Oncorus plans to file an IND for ONCR-788 to enable its development in small cell lung cancer, neuroendocrine prostate and other neuroendocrine cancers, both as a single agent and in combination with immune checkpoint inhibitors and other cancer treatments. In the process of developing ONCR-021 and ONCR-788, Oncorus also developed and optimized a proprietary LNP platform for delivery of large nucleic acids, with efficient

endosomal escape. Oncorus will manufacture ONCR-021 and ONCR-788 at its 88,000 square foot state-of-the-art process development and Good Manufacturing Practices (GMP) manufacturing facility in Andover, Mass. With the site buildout underway, Oncorus plans to initiate process development activities at the facility in the second half of 2021 and anticipates this facility will be operational for GMP manufacturing in first half of 2023.

Link here to a white paper on Oncorus’ Synthetic vRNA Immunotherapy Platform and lead candidates.

Upcoming Synthetic vRNA Immunotherapy-Focused Investor Event

Oncorus will host a virtual investor event on Monday, June 21, 2021 from 1:00 pm to 3:30 pm ET to discuss details surrounding these Synthetic vRNA programs, including preclinical data supporting the ONCR-021 and ONCR-788 candidate nominations and planned clinical studies. Leena Ghandi, M.D., Ph.D., Director, Center for Cancer Therapeutic Innovation at the Dana-Farber Cancer Institute, will be a featured speaker. For more information or to RSVP for the event, please contact Josh Rauch at [email protected].

On May 27, 2021 BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) reported that management will participate in two upcoming virtual conferences (Press release, BioMarin, MAY 27, 2021, View Source [SID1234583249]). An audio webcast of the presentations will be available live. You can access the webcast at: View Source An archived version of the remarks will also be available through the Company’s website for a limited time following the conference.

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