On December 7, 2020 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company") reported that safety data from its ongoing pivotal Phase 3 SIERRA trial of Iomab-B in patients with relapsed or refractory Acute Myeloid Leukemia (R/R AML) were presented at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting (Press release, Actinium Pharmaceuticals, DEC 7, 2020, View Source [SID1234572353]). The oral presentation highlighted Iomab-B’s targeting ability and corresponding safety data from 110 patients from the SIERRA trial for which detailed safety data was available. Iomab-B targets CD45, an antigen expressed on leukemia and lymphoma cancer cells and immune cells including bone marrow stem cells but not cells outside of the blood forming or hematopoietic system. This allows high amounts of radiation to be delivered to the bone marrow via Iomab-B while sparing healthy organs. As a result, statistically significant lower rates of sepsis were reported as well as lower rates of febrile neutropenia, mucositis and non-relapse transplant related mortality in patients receiving Iomab-B and bone marrow transplant (BMT) compared to patients that received salvage therapy and a BMT. In addition, patients that crossed over to receive Iomab-B and went to BMT after receiving salvage therapy but not achieving a complete response also had lower rates of sepsis, febrile neutropenia, mucositis and non-relapse transplant related mortality.

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Dr. Mark Berger, Actinium’s Chief Medical Officer, commented, "We are pleased that the engraftment and safety profile of Iomab-B remains positive and consistent with prior interim safety results at 75% of patient enrollment in SIERRA and also consistent with the large body of historical data from Iomab-B. Collectively, this data gives excitement as we approach the upcoming ad hoc interim analysis for SIERRA that will be completed by year-end and the ultimate potential of Iomab-B for patients with R/R AML and other blood cancers as a targeted conditioning regimen."

Safety data presented in ASH (Free ASH Whitepaper) oral presentation are highlighted in the table below:

ASH Oral Presentation: High Doses of Targeted Radiation with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] Do Not Correlate with Incidence of Mucositis, Febrile Neutropenia or Sepsis in the Prospective, Randomized Phase 3 Sierra Trial for Patients with Relapsed or Refractory Acute Myeloid Leukemia

Adverse Event

1 Adverse Event data available for 46 of 47 evaluable patients

2 Adverse Event data available for 27 of 30 evaluable patients

3 Iomab-B arm: 4 patients unevaluable. Conventional Care Arm: 4 patients unevaluable

Patient Group

No. of
Patients

Radiation dose delivered to
the Marrow. Median (range)

Radiation dose to GI tract.
Median (range)

Iomab-B

Vijay Reddy, Vice President, Clinical Development and Head of BMT, "The targeted nature of Iomab-B makes it highly differentiated from current BMT conditioning regimens that are largely comprised of non-targeted cytotoxic chemotherapies. These data from SIERRA showing higher rates of sepsis, neutropenia and mucositis in patients receiving chemotherapy are consistent with the literature and unfortunately what we expected but hope to address with Iomab-B. Particularly, chemotherapy’s effect on the GI tract and resulting mucositis, which we believe is leading to the higher rates of sepsis seen in the control arm. We are highly encouraged by the lower rates of adverse events and the universal engraftment reported from SIERRA and excited for the potential of targeted conditioning could have an BMT access, patient outcomes and quality of life."

About Iomab-B

Iomab-B (I-131 apamistamab) via the monoclonal antibody apamistamab, targets CD45, an antigen widely expressed on leukemia and lymphoma cancer cells, B cells and stem cells. Apamistamab is linked to the radioisotope iodine-131 (I-131) and once attached to its target cells emits energy that travels about 100 cell lengths, destroying a patient’s cancer cells and ablating their bone marrow. By carrying iodine-131 directly to the bone marrow in a targeted manner, Actinium believes Iomab-B will avoid the side effects of radiation on most healthy tissues while effectively killing the patient’s cancer and marrow cells.

Iomab-B is currently being studied in the pivotal Phase 3 SIERRA (Study of Iomab-B in Relapsed or Refractory AML) trial, a 150-patient, randomized controlled clinical trial in patients with relapsed or refractory Acute Myeloid Leukemia (AML) who are age 55 and above. The SIERRA trial is being conducted at preeminent transplant centers in the U.S. with the primary endpoint of durable Complete Remission (dCR) at six months and a secondary endpoint of overall survival at one year. Upon approval, Iomab-B is intended to prepare and condition patients for a bone marrow transplant, also referred to as a hematopoietic stem cell transplant, in a potentially safer and more efficacious manner than the non-targeted intensive chemotherapy conditioning that is the current standard of care in bone marrow transplant conditioning. A bone marrow transplant is often considered the only potential cure for patients with certain blood-borne cancers and blood disorders. Additional information on the Company’s Phase 3 clinical trial in R/R can be found at www.sierratrial.com.

On December 7, 2020 OncoMyx Therapeutics, a privately-held oncolytic immunotherapy company, reported that The University of Western Ontario (Western) has assigned to OncoMyx the technology and patent rights associated with pioneering research on the use of myxoma virus in the treatment of cancer (Press release, OncoMyx Therapeutics, DEC 7, 2020, View Source [SID1234572370]). This research was led by OncoMyx cofounder Grant McFadden, Ph.D., when he was a Professor at Western and the Robarts Research Institute.

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Lisa Cechetto, the Executive Director of WORLDiscoveriesTM, the technology transfer office for Western, Robarts Research Institute, and Lawson Research Institute, said, "We are pleased to assign these patents to OncoMyx, as it is important that the outputs of pioneering research, such as Dr. McFadden’s use of myxoma virus to create novel oncolytic therapies, be further developed to improve the lives of cancer patients or others who may benefit."

"The assignment of this technology and intellectual property to OncoMyx further reinforces our IP portfolio protecting our use of myxoma virus and our pipeline of myxoma virotherapies for the treatment of cancer," said Steve Potts, Ph.D., MBA, cofounder and chief executive officer of OncoMyx. "The myxoma virus has a number of important attributes that we are leveraging to develop potentially impactful oncolytic immunotherapies with the goal of increasing the number of cancer patients who could benefit from immunotherapies."

"Oncolytic viruses are emerging as a new pillar of cancer care with the potential to expand the effectiveness of immunotherapies, such as immune checkpoint inhibitors," said Dr. McFadden. "I am pleased that OncoMyx has been assigned the patent rights associated with the pioneering myxoma research that was done at Western, as the myxoma virus is unique as a technology platform to build oncolytic immunotherapies."

About Myxoma Virotherapy for the Treatment of Cancer

The myxoma virus is highly immuno-interactive and can selectively infect and kill a broad range of cancer cell types. Because myxoma virus is not pathogenic to humans, myxoma virotherapy does not have to overcome pre-existing immunity. As a large dsDNA poxvirus, myxoma is engineerable to express multiple transgenic payloads, such as immunomodulatory proteins, to target multiple points in the cancer immunity cycle. The company’s preclinical data demonstrates efficacy of multi-armed myxoma virotherapies via intravenous (IV) and intratumoral (IT) delivery in a number of tumor models across multiple cancer indications and supports a pan-tumor approach to expand the therapeutic effectiveness of immunotherapies.

On December 7, 2020 Menarini Group reported that it will present the results of two different preclinical studies on MEN1611, a potent and selective phosphatidylinositol 3-kinase inhibitor (PI3Ki) currently in clinical development for the treatment of breast cancer, at the upcoming 2020 San Antonio Breast Cancer Symposium, which will be held virtually on December 8-11 (Press release, Menarini, DEC 7, 2020, View Source [SID1234572389]).

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"We are pleased to present at the San Antonio Breast Cancer Symposium and look forward to discussing in more detail the encouraging preliminary results achieved by our preclinical studies on MEN1611," commented Andrea Pellacani, General Manager of Menarini Ricerche, R&D Division of the Menarini Group. "This data contributes to a greater understanding of the mechanism of action of MEN1611 and further support its clinical development for the treatment of breast cancer, reinforcing our strong commitment to advancing precision oncology to the benefit of patients living with difficult-to-treat cancer."

MEN1611 is a potent and selective PI3Ki targeting the p110 α, β and γ isoforms, while sparing the δ subunit. B-PRECISE-01 is a multicenter, Phase Ib, dose escalation and expansion study, investigating MEN1611 in patients with HER2-positive, PIK3CA mutated, advanced or metastatic breast cancer.

The poster entitled "MEN1611 is a PI3K α/β selective and δ sparing inhibitor with long-lasting antitumor activity in different genetic backgrounds of PIK3CA mutant breast cancer models" presents the results of a preclinical study on the antitumor activity of MEN1611 in p110 α- and β-dependent tumors, providing evidence that in these animal models MEN1611 is active against HER2-positive, PIK3CA mutated and PTEN-null breast tumor.

A second poster, entitled "MEN1611 promotes immune activating myeloid cell polarization" presents the results of a study aimed at characterizing the effects of MEN1611 on the PI3Kγ isoform, highly expressed in tumor-associated macrophages, to investigate whether the anti-tumor activity of MEN1611 might also be mediated by MEN1611-mediated modulation of tumor inflammatory microenvironment. The results of this study show that MEN1611 inhibition of the PI3Kγ isoform leads to macrophage reprogramming, from an immune-suppressive to an immune-activating phenotype. Moreover, the tumor regression induced by MEN1611 was associated to changes of the inflammatory microenvironment, characterized by an increased recruitment of T cells, which may contribute to the anti-tumor activity of MEN1611 in this model.

About MEN1611

MEN1611 is a potent and selective PI3K inhibitor targeting the p110 α, β and γ isoforms, while sparing the δ subunit. It is an investigational compound, not approved for use by regulatory authorities, currently being evaluated in the B-PRECISE-01 trial (clinicaltrials.gov identifier: NCT03767335), and in the C-PRECISE-01 trial (clinicaltrials.gov identifier: NCT04495621) for the treatment of breast cancer and colorectal cancer, respectively.

On December 7, 2020 BridgeBio Pharma, Inc. (Nasdaq: BBIO) and Maze Therapeutics reported the establishment of a joint venture, Contour Therapeutics, focused on transforming and advancing breakthrough precision medicine approaches designed to treat cardiovascular disease, the leading cause of death worldwide (Press release, BridgeBio, DEC 7, 2020, View Source [SID1234576219]).

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This joint venture between two leading biotech companies unites Maze’s genetically driven approach to drug discovery, as well as insights from its COMPASS platform, with BridgeBio’s expertise in cardiac drug discovery and clinical development. Together, the companies will focus on advancing genetically validated therapeutic candidates through clinical development and will initially work on the development of a treatment for patients with an undisclosed, genetically defined form of heart failure.

The new partnership builds on exciting progress underway to identify and target genetic causes of cardiovascular diseases, including BridgeBio’s precision medicine approach at its affiliate Eidos Therapeutics designed to treat transthyretin amyloidosis, an underdiagnosed and life-threatening cause of heart failure. The partnership also builds on seminal advances in the treatment of inherited cardiomyopathies, including at MyoKardia, a company co-founded by senior leaders at BridgeBio and Maze.

"Cardiovascular disease is a deadly and widespread health problem across the world, but unfortunately, innovations in new treatment approaches have been limited," said Jason Coloma, Ph.D., CEO of Maze. "Since we launched Maze, we have been focused on the advancement of our COMPASS platform, on which we’ve made important progress and gained confidence in the genetics we are focused on, as well as novel insights into how to best develop therapies for patients with cardiovascular disease. We are excited to join forces with BridgeBio, combining the unique talents and expertise across our respective teams, in order to deliver a profound impact on how these diseases are treated in the future."

"We are privileged to be partnering with and learning from Maze. We are eager to build on BridgeBio’s work in precision medicine to treat cardiovascular disease, and we believe our joint venture with Maze holds great promise for patients as we bring together innovative leaders in cardiology and genetics," said Neil Kumar, Ph.D., founder and CEO of BridgeBio. "The identification and targeting of genetically defined patient populations has created elegant and clinically meaningful medicines in oncology and other therapeutic areas. We feel strongly that one of the next frontiers in precision medicine lies in helping people suffering from cardiovascular disease, and we are excited to be on the front lines of advances in this field."

"This partnership between Maze and BridgeBio will bring together many of the people who helped found and build revolutionary companies in cardiovascular drug development," said Charles Homcy, M.D., chairman of the Maze board of directors and lead director and chairman of pharmaceuticals of BridgeBio. "With the combined expertise of these teams, we have an opportunity to create something special that has a profound impact on how patients with cardiovascular disease are treated in the future."

About the Maze COMPASS Platform
The Maze COMPASS platform combines human genetics, functional genomics and data science to identify and prioritize drug targets for both rare and common diseases, validate drug targets and inform target tractability and clinical development. Maze aims to leverage COMPASS to translate a wealth of genetic opportunities generated by the platform into new therapeutics.

On December 7, 2020 TG Therapeutics, Inc. (NASDAQ: TGTX), reported two triple therapy combination data presentations (Press release, TG Therapeutics, DEC 7, 2020, View Source [SID1234572320]). The first evaluated the investigational combination of umbralisib plus ublituximab (U2) plus venetoclax in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL); and the second evaluated the investigational combination of U2 plus TG-1701, the Company’s once daily, oral, BTK inhibitor, in patients with R/R CLL or B-cell lymphoma. Data from these trials were presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting and exposition. Presentation highlights are included below.

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, stated, "We are extremely pleased by the triple therapy data presented today demonstrating the potential of U2 with both venetoclax and our BTK inhibitor, TG-1701." Mr. Weiss continued, "Our mission continues to be to drive toward better outcomes for patients with B-cell malignancies by developing multi-drug combinations. We believe the data with these triple combinations highlights our approach of leveraging our portfolio and standard of care therapies to build on the U2 backbone with the goal of creating potentially best in class treatments for patients in need."

PRESENTATION HIGHLIGHTS:

Poster Presentation Title: A Phase 1/2 Study of Umbralisib, Ublituximab, and Venetoclax (U2-Ven) in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Regimen was administered with 3 cycles of U2 as induction in cycles 1 through 3, U2 plus venetoclax in cycles 4, 5 and 6, followed by umbralisib plus venetoclax in cycles 7 through 12 in patients with R/R CLL. Patients with centrally confirmed undetectable minimal residual disease (uMRD) in the bone marrow after cycle 12 were permitted to stop all therapy, while MRD detectable patients continued on single agent umbralisib.
43 patients have been treated as of the data cutoff with 58% of patients previously exposed to a BTK inhibitor
Among evaluable patients, ORR was 77% (30/39) after cycle 3 (U2 only), 100% (31/31) after cycle 7, and 100% (27/27) after cycle 12
Among the 27 patients who finished 12 cycles of therapy:
• 41% achieved Complete Response (CR) by iwCLL criteria
• 96% achieved undetectable MRD in the peripheral blood
• 77% achieved undetectable MRD in the bone marrow
At a median follow up of 15.6 months (n=43), only 1 patient has progressed 10 months after stopping treatment
Grade 3/4 adverse events occurring in > 5% of patients were neutropenia (21%), leukopenia (12%), infusion related reactions (7%), anemia (5%), and diarrhea (5%). No TLS events were observed during venetoclax administration, with one TLS event occurring prior to venetoclax administration.
Poster Presentation Title: Clinical Activity of TG-1701, As Monotherapy and in Combination with Ublituximab and Umbralisib (U2), in Patients with B-Cell Malignancies

A total of 102 patients with R/R CLL or b-cell lymphoma have been treated with TG-1701, with patients receiving monotherapy in the dose-escalation cohort (n=25) or in the 200 mg dose-expansion cohort (n=61), or TG-1701 in combination with U2 in the dose escalation cohort (n=16)
TG-1701 monotherapy was well tolerated and the maximum tolerated dose was not reached up through 400 mg QD
Grade 3/4 adverse events (AE) occurring in >10% of patients treated with TG-1701 monotherapy were limited and included ALT increase (12%), all of which were patients treated with 400 mg QD. At the target single-agent Phase 2 dose of 200mg (QD) (n=61), AEs of special interest included Grade 3 hypertension (1.6%), atrial fibrillation (1.6%), and no instances of major bleeding observed. Grade 3/4 AEs occurring in >10% of patients treated with U2+1701 were ALT increase (25%), AST increase (19%) and neutropenia (12%).
At a median follow up of 7 months in the 200 mg QD monotherapy expansion cohorts, preliminary overall response rates (ORR) were: 95% (19/20) in CLL, 50% (6/12) in mantle cell lymphoma (MCL), and 95% (18/19) in Waldenstrom macroglobulinemia (WM)
At a median follow up of 12 months, the 1701+U2 dose escalation (using doses of 100mg to 300 mg QD of TG-1701) resulted in 79% ORR, with 22% CR rate across patients with WM, CLL, marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) (n=14)
Data presented at ASH (Free ASH Whitepaper) 2020 will be available on the Publications page of the Company’s website at View Source

CONFERENCE CALL REPLAY INFORMATION
The Company hosted a conference call on November 5, 2020, with leading investigators from the UNITY-NHL and UNITY-CLL trials to discuss the data included in the ASH (Free ASH Whitepaper) 2020 abstracts. A recording of the conference call is available for replay at View Source