On October 6, 2020 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company") reported that the University of Louisville and the Ochsner Clinic in New Orleans, Louisiana are now active trial sites in its Phase 1/2 Actimab-A venetoclax combination trial for patients with Relapsed or Refractory ("R/R") Acute Myeloid Leukemia ("AML") age 18 and above (Press release, Actinium Pharmaceuticals, OCT 6, 2020, View Source [SID1234568155]). These sites join UCLA Medical Center, where the trial is being led by Gary Schiller, MD, Professor, Hematology-Oncology and Director, Hematologic Malignancy/Stem Cell Transplant Program. Both sites participated in Actinium’s Phase 2 trial with Actimab-A as a single agent that produced remission rates as high as 69% with minimal non-hematologic toxicities in patients newly diagnosed with AML. The Phase 2 trial results together with a synergistic mechanism of action with venetoclax demonstrated in pre-clinical studies are driving this combination trial with an initial focus on the high unmet needs of R/R patients including those who have relapsed or do not respond to treatment with venetoclax based regimens.

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"Venetoclax is now a mainstay in the AML treatment armamentarium, but the lack of durable remissions, particularly in patients with relapsed or refractory disease who may not respond to venetoclax at all, is an area we are committed to addressing. Our pre-clinical data indicate that Actimab-A is synergistic with venetoclax in venetoclax-resistant cell lines and have documented a reduction of Mcl-1 as the mechanism. Our clinical trial seeks to demonstrate improved response rates and response durations without added toxicities with the combination of Actimab-A and venetoclax. Given the preclinical data, the targeted nature of Actimab-A, and the minimal non-hematologic toxicity profile, we think that the combination with venetoclax has great promise" said Dr. Mark Berger, Actinium’s Chief Medical Officer. Dr. Berger added, "We are delighted to once again be working with the University of Louisville and the Ochsner Clinic who were among the top enrolling sites in our Phase 2 single-agent Actimab-A trial. We look forward to activating additional sites on this important trial as we work to advance treatment options for patients with AML."

Actinium recently announced that the first dose cohort in the Phase 1 portion of the Actimab-A venetoclax combination trial has been complete and enrollment of the second dose cohort has been initiated. Actinium expects continued site additions and anticipates proof of concept results from the Phase 1 portion of the trial in 2021.

Rationale for Actimab-A Venetoclax Combination Trial

This Phase 1/2 trial is a multicenter, open label trial of Actimab-A (lintuzumab-Ac225) added to venetoclax for patients with CD33 positive relapsed/refractory (R/R) Acute Myeloid Leukemia. In a poster presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019, Actimab-A was shown to be synergistic with venetoclax in venetoclax resistant cell lines, by depleting MCL-1, a protein shown to mediate resistance to venetoclax. The Phase 1 portion of the study is designed to determine the maximum tolerated dose (MTD) of Actimab-A added to venetoclax for R/R AML. The Phase 2 portion of the trial will assess the percentage of patients with Overall Response (CR + CRh) up to six months after the start of the treatment without receiving other AML therapies. The trial will enroll R/R AML patients who have been treated with venetoclax as well as venetoclax-naïve patients. At the 1.0 uCi/kg dose, Actimab-A is administered on Day 5 of each cycle for four cycles and venetoclax is taken on Days 1-21 of each cycle for up to 4 cycles. Each cycle is 28 days, with a potential to expand to 42 days to allow for full hematologic recovery. Gary Schiller, MD, Professor, Hematology-Oncology and Director, Hematologic Malignancy/Stem Cell Transplant Program at the UCLA Medical Center is the Principal Investigator for this study.

On October 6, 2020 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported that the first patient was successfully dosed with allogeneic cord blood-derived natural killer (cbNK) cells preloaded with AFM13 and has moved on to the AFM13 monotherapy phase of the treatment cycle (Press release, Affimed, OCT 6, 2020, View Source [SID1234568154]). This therapy was developed through a research collaboration with The University of Texas MD Anderson Cancer Center.

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This is the first in human study to combine an NK cell product with an antibody whose primary mechanism is designed to specifically bind and activate NK cells and tumors cells in a bispecific fashion. This novel combination approach could lay the groundwork for future cellular therapy combinations with Affimed ICE constructs.

"Engaging the innate immune system is a novel and promising therapeutic approach in oncology and our ICE products are designed to tap into this, which, thus far, has largely remained untapped in this field," said Dr. Andreas Harstrick, Chief Medical Officer at Affimed. "Pre-loading innate immune cells with an ICE takes this idea a step further and potentially intensifies the treatment’s effect, especially in patients who have an impaired immune system or low NK cell numbers."

An NK cell armed with AFM13 is designed to direct NK cells to the tumor site in order to target cancer cells. Pursuant to the study design, after dosing with the preloaded NK cells, AFM13 is subsequently administered as monotherapy in order to maintain the activation of the infused cbNK cells and engage the patients’ own innate immune system (NK cells and macrophages), a distinct feature of Affimed’s ICE products.

Further Study Background
Although larger numbers of NK cells in patients is associated with better outcomes, the adoptive transfer of non-targeted NK cells has shown only limited clinical benefit. Target recognition of cancers by NK cells remains a substantial barrier to broad application of an NK cell therapy. In preclinical models, combining AFM13 with adoptive NK cell transfer has been shown to enhance the efficacy of NK cells. AFM13 exhibited a much longer binding to CD16A on NK cells as compared to CD30 binding monoclonal antibodies, both wildtype and ADCC enhanced, forming the basis to produce a stable AFM13 pre-loaded NK cell product. The study, which aims to enroll approximately 30 patients, is an investigator-initiated study at MD Anderson. The study is an open-label, non-randomized, single-center, dose escalation trial to evaluate the combination of AFM13 with cord blood-derived NK cells in adult patients with recurrent/refractory CD30-positive lymphomas. The primary objective of the study is to establish the safety and the recommended Phase 2 dose of AFM13-preloaded cbNK cells, followed by weekly treatment with intravenous AFM13. Secondary objectives include assessing the overall, complete and partial response rates. More details about the study can be found at www.clinicaltrials.gov using the identifier NCT04074746.

About AFM13
AFM13 is a first-in-class CD30/CD16A ROCK-derived bispecific innate cell engager (ICE) that induces specific and selective killing of CD30-positive tumor cells by engaging and activating natural killer (NK) cells and macrophages, thereby leveraging the power of the innate immune system. AFM13 is Affimed’s most advanced ICE clinical program, and it is currently being evaluated as a monotherapy in a registration-directed trial in patients with relapsed/refractory peripheral T-cell lymphoma (REDIRECT). The study is actively recruiting and can be found at www.clinicaltrials.gov using the identifier NCT04101331.

On October 6, 2020 Neurocrine Biosciences, Inc. (Nasdaq: NBIX) reported that it will report third quarter financial results after the Nasdaq market closes on Monday, November 9, 2020 (Press release, Neurocrine Biosciences, OCT 6, 2020, View Source [SID1234568152]). Neurocrine will then host a conference call and webcast to discuss its financial results and provide a company update that day at 1:30 p.m. Pacific Time (4:30 p.m. Eastern Time).

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Participants can access the live conference call by dialing 877-830-2596 (US) or 785-424-1744 (International) using the conference ID: NBIX. The webcast can also be accessed on Neurocrine’s website under Investors at www.neurocrine.com. A replay of the webcast will be available on the website approximately one hour after the conclusion of the event and will be archived for approximately one month.

On October 6, 2020 The National Institutes of Health reported that it has awarded 85 grants through its High-Risk, High-Reward Research (HRHR) Program that will fund highly innovative and unusually impactful biomedical or behavioral research proposed by extraordinarily creative scientists (Press release, US NIH, OCT 6, 2020, View Source [SID1234568151]). Examples of supported research include understanding the role of neighborhoods on urban substance abuse, brain-machine interfaces that allow learning by both brain and machine, engineering multi-organs in a dish, and exploiting latent immune pathways to treat disease. The 85 awards total approximately $251 million over five years, pending available funds.

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The High-Risk, High-Reward Research program catalyzes scientific discovery by supporting research proposals that, due to their inherent risk, may struggle in the traditional peer-review process despite their transformative potential. Program applicants are encouraged to think "outside the box" and to pursue trailblazing ideas in any area of research relevant to the NIH’s mission to advance knowledge and enhance health.

"The breadth of innovative science put forth by the 2020 cohort of early career and seasoned investigators is impressive and inspiring," said NIH Director Francis S. Collins, M.D., Ph.D. "I am confident that their work will propel biomedical and behavioral research and lead to improvements in human health."

The High-Risk, High-Reward Research Program is part of the NIH Common Fund, which oversees programs that pursue major opportunities and gaps throughout the research enterprise that are of great importance to NIH and require collaboration across the agency to succeed. The High-Risk, High-Reward Research program manages the following four awards, including two awards aimed specifically to support researchers in the early stages of their careers:

The NIH Director’s Pioneer Award, established in 2004, challenges investigators at all career levels to pursue new research directions and develop groundbreaking, high-impact approaches to a broad area of biomedical, behavioral, or social science.
The NIH Director’s New Innovator Award, established in 2007, supports unusually innovative research from early career investigators who are within 10 years of their final degree or clinical residency and have not yet received a research project grant or equivalent NIH grant.
The NIH Director’s Transformative Research Award, established in 2009, promotes cross-cutting, interdisciplinary approaches and is open to individuals and teams of investigators who propose research that could potentially create or challenge existing paradigms.
The NIH Director’s Early Independence Award, established in 2011, provides an opportunity to support exceptional junior scientists who have recently received their doctoral degree or completed their medical residency to skip traditional post-doctoral training and move immediately into independent research positions.
NIH issued 10 Pioneer awards, 53 New Innovator awards, nine Transformative Research awards, and 13 Early Independence awards for 2020. Funding for the awards comes from the NIH Common Fund; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Cancer Institute; National Human Genome Research Institute; National Institute of Biomedical Imaging and Bioengineering; National Institute of Dental and Craniofacial Research; National Institute of General Medical Sciences; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; and National Institute on Aging.

On October 6, 2020 Integra LifeSciences Holdings Corporation (NASDAQ: IART), a leading global medical technology company,reported certain unaudited preliminary third quarter financial results (Press release, Integra LifeSciences, OCT 6, 2020, View Source [SID1234568150]). The company also announced that it will release full third quarter 2020 financial results on Wednesday, October 28, 2020 at 8:30 a.m. ET.

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Preliminary Third Quarter Revenue Results

Third quarter 2020 reported revenue is expected to be in the range of $368 million to $370 million, representing a decline of approximately 2.7% on a reported basis and approximately 1.8% on an organic basis compared to the third quarter of 2019.

These results exceeded the Company’s third quarter revenue outlook range provided in August during the second quarter conference call and represent a significant recovery from the second quarter decline of 32.6%. The sales improvement in the third quarter was broad-based across the Company’s major franchises. The preliminary results set forth above are unaudited and remain subject to completion of the Company’s financial closing procedures.

Third Quarter 2020 Financial Results Conference Call

The Company will release full third quarter 2020 financial results on Wednesday, October 28, 2020 before the market opens. In conjunction with the earnings release, Integra’s management team will host a conference call at 8:30 a.m. ET.
The live call is accessible by dialing (800) 353-6461 and using the passcode 9501226. A simultaneous webcast of the call will be available via the Company’s website at www.integralife.com.
A webcast replay of the call can be accessed through the Investor Relations homepage of Integra’s website at www.integralife.com. A replay of the call will be available until November 2, 2020 by dialing (888) 203-1112 and using the passcode 9501226.