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 Sesen Bio (Nasdaq: SESN), a late-stage clinical company developing targeted fusion protein therapeutics for the treatment of patients with cancer, reported that on Friday, December 4, 2020 the Company entered into a commercial manufacturing and supply framework agreement (the "CMO Agreement") with the Company’s partner in China, Qilu Pharmaceutical Co., Ltd. ("Qilu") (Press release, Sesen Bio, DEC 7, 2020, View Source [SID1234572352]).

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Under the CMO Agreement, Qilu will be part of the contract manufacturing network for global commercial supply of Vicineum. The Company’s lead program, Vicineum, is currently in the follow-up stage of a Phase 3 registration trial in the United States ("US") for the treatment of high-risk, BCG-unresponsive non-muscle invasive bladder cancer ("NMIBC"). The Company is on track to complete the BLA for Vicineum and submit to the FDA later this month.

In July 2020, the Company and Qilu entered into an agreement which grants Qilu an exclusive license to develop, manufacture and commercialize Vicineum in China.

"NMIBC is a disease area that has chronically suffered from manufacturing and CMC issues with significant impacts on patient care," said Dr. Thomas Cannell, president and chief executive officer of Sesen Bio. "Given this, we have taken a thoughtful approach to our supply chain and partnerships in order to meet the significant anticipated global demand for Vicineum. Qilu has a large and experienced manufacturing team and currently supplies products for commercial sale around the world. The CMO Agreement represents an exciting expansion of our strong partnership with Qilu and will help Sesen Bio to reliably meet the projected global demand, while also creating an opportunity to reduce the cost of goods."

The Company believes that the technology transfer to Qilu for manufacturing of Vicineum is on track to be completed in mid-2021. Upon completion of the technology transfer, Sesen Bio is entitled to receive a $2M milestone payment.

In addition to Fujifilm and Baxter, the CMO partnership with Qilu expands the Company’s network of world-class partners committed to providing reliable supply of Vicineum around the world.

About Vicineum

Vicineum, a locally administered fusion protein, is Sesen Bio’s lead product candidate being developed for the treatment of high-risk non-muscle invasive bladder cancer (NMIBC). Vicineum is comprised of a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas Exotoxin A. Vicineum is constructed with a stable, genetically engineered peptide tether to ensure the payload remains attached until it is internalized by the cancer cell, which is believed to decrease the risk of toxicity to healthy tissues, thereby improving its safety. In prior clinical trials conducted by Sesen Bio, EpCAM has been shown to be overexpressed in NMIBC cells with minimal to no EpCAM expression observed on normal bladder cells. Sesen Bio is currently conducting the Phase 3 VISTA trial, designed to support the registration of Vicineum for the treatment of high-risk NMIBC in patients who have previously received a minimum of two courses of bacillus Calmette-Guérin (BCG) and whose disease is now BCG-unresponsive. Additionally, Sesen Bio believes that cancer cell-killing properties of Vicineum promote an anti-tumor immune response that may potentially combine well with immuno-oncology drugs, such as checkpoint inhibitors. The activity of Vicineum in BCG-unresponsive NMIBC is also being explored at the US National Cancer Institute in combination with AstraZeneca’s immune checkpoint inhibitor durvalumab.

On December 7, 2020 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported updated interim clinical data from the ongoing Phase 1/2 CIRLL (Cirmtuzumab and Ibrutinib targeting ROR1 for Leukemia and Lymphoma) clinical trial, in which cirmtuzumab, an investigational anti-ROR1 monoclonal antibody, is being evaluated in combination with ibrutinib in patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) (Press release, Oncternal Therapeutics, DEC 7, 2020, View Source [SID1234572351]). The clinical trial is being partially funded by the California Institute for Regenerative Medicine. The data were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2020 Virtual Annual Meeting, and a copy of the poster presentation is available online at www.oncternal.com:

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Abstract Title: Cirmtuzumab, an Anti-ROR1 Antibody, in Combination with Ibrutinib: Clinical Activity in Mantle Cell Lymphoma (MCL) or Chronic Lymphocytic Leukemia (CLL) from a Phase 1/2 Study (abstract # 2942)
Session Title: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma – Clinical Studies: Poster III
Session Date and Time: December 7, 2020, 7:00 a.m. – 3:30 p.m. (Pacific Time)
"The interim data from the combination of cirmtuzumab and ibrutinib are quite promising in relapsed/refractory (r/r) MCL, with an impressive 87% best ORR that has improved over time. The time to response, depth and durability of responses make cirmtuzumab a compelling candidate for further development," said Hun Ju Lee, M.D., Associate Professor of Medicine in the Department of Lymphoma & Myeloma at the University of Texas MD Anderson Cancer Center, who is an investigator on the CIRLL clinical trial and was also the first author on the 2020 ASCO (Free ASCO Whitepaper) poster presentation.

"We are pleased that median PFS has not yet been reached after a median follow-up of over 12 months in the MCL patients, and are encouraged that both PFS and ORR have improved with longer follow-up," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "We are in active dialogue with FDA on pivotal study design in order to define the path to approval in MCL."

As of the data cut-off date of October 30, 2020, 15 patients with relapsed/refractory MCL enrolled in the dose-finding and dose-expansion cohorts of this clinical trial were evaluable for efficacy:

The overall best objective response rate (ORR) was 87% (13 of 15 evaluable patients), improved over the 83% ORR reported at ASCO (Free ASCO Whitepaper) 2020.
The complete response (CR) rate, determined by Cheson criteria, remains 57% (7 of 12 evaluable patients) for Part 1 of the study, and is 47% (7 of 15 evaluable patients) for Part 1 + Part 2, including the three patients from Part 2 who have shorter followup. One of the seven patients had a complete metabolic response (CMR) as assessed by PET scan, with an indeterminate bone marrow biopsy on blinded review. All complete responses remained durable, ranging from 5-25 months as of the cutoff date, with no progressions reported after achieving a CR. Six patients (40%) achieved a partial response (PR). In addition, two patients had stable disease (SD), for a total best clinical benefit rate (CR, PR and SD) of 100%.
Median progression-free survival (PFS) was not reached, with the 95% confidence interval above 17.5 months, after a median follow-up of 12.1 months.
Patients had received a median of two prior therapies (range 1-5) before participating in this clinical trial, with 73% of patients with two or more prior lines of therapy. Four patients had received prior treatment with ibrutinib and all four achieved clinical responses in this clinical trial, with two CRs and two PRs. Fourteen of the 15 evaluable patients (93%) had high or intermediate MCL International Prognostic Index (MIPI-b) risk score at study entry.
Historical data published for single-agent ibrutinib for 370 patients with r/r MCL, who had received a median of two prior therapies, reported an ORR of 66%, CR rate of 20%, PR rate of 46%, and median PFS of 12.8 months (Rule et al., 2017, British Journal of Haematology).
As of the data cut-off date on October 30, 2020, 56 evaluable patients with CLL were enrolled in the dose-finding, dose-confirming and randomized cohorts of this clinical trial, 49 of whom were treated with the combination of cirmtuzumab and ibrutinib:

Forty-five of the 49 patients achieved a clinical response, for an overall best objective response rate of 92%, including one patient who achieved a CR. In addition, four patients had stable disease, for a total clinical benefit rate (CR, PR, and SD) of 100%.
The median PFS was not reached for patients with treatment-naïve CLL (n=19) after a median follow-up of 16.6 months, and median PFS was 29.5 months for patients with r/r CLL (n=30) after a median follow-up of 17.1 months.
The combination of cirmtuzumab plus ibrutinib has been well tolerated, with adverse events consistent with those reported for ibrutinib alone. There have been no dose-limiting toxicities and no serious adverse events attributed to cirmtuzumab alone.

About the CIRLL Clinical Trial
The CIRLL clinical trial (CIRM-0001) is a Phase 1/2 trial evaluating cirmtuzumab in combination with ibrutinib in separate groups of patients with CLL or MCL. Enrollment of the dose-finding cohorts in CLL and MCL, dose-expansion cohort in CLL and randomized Phase 2 cohort in CLL has been completed. Enrollment of the dose-expansion cohort in MCL is ongoing. Additional information about the CIRM-0001 clinical trial and other clinical trials of cirmtuzumab may be accessed at ClinicalTrials.gov.

About Cirmtuzumab
Cirmtuzumab is an investigational, potentially first-in-class monoclonal antibody targeting ROR1, or Receptor tyrosine kinase-like Orphan Receptor 1. Cirmtuzumab is currently being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of CLL or MCL, in a collaboration with the University of California San Diego (UC San Diego) School of Medicine and the California Institute for Regenerative Medicine (CIRM). In addition, an investigator-initiated Phase 1 clinical trial of cirmtuzumab in combination with paclitaxel for women with metastatic breast cancer is being conducted at the UC San Diego School of Medicine.

ROR1 is a potentially attractive target for cancer therapy because it is an onco-embryonic antigen – not usually expressed on adult cells, and its expression confers a survival and fitness advantage when reactivated and expressed by tumor cells. Researchers at the UC San Diego School of Medicine discovered that targeting a critical epitope on ROR1 was key to specifically targeting ROR1 expressing tumors. This led to the development of cirmtuzumab, that binds this critical epitope of ROR1, which is highly expressed on many different cancers but not on normal tissues. Preclinical data showed that when cirmtuzumab bound to ROR1, it blocked Wnt5a signaling, inhibited tumor cell proliferation, migration and survival, and induced differentiation of the tumor cells. The FDA has granted Orphan Drug Designations to cirmtuzumab for the treatment of mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma. Cirmtuzumab is in clinical development and has not been approved by the FDA for any indication.

On December 7, 2020 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers, reported that it has been notified by the U.S. Food and Drug Administration (FDA) that a clinical hold has been placed on patient enrollment and dosing in an ongoing Phase 1/2 dose-escalation clinical trial evaluating BPX-601 in patients with previously treated metastatic pancreatic or prostate cancer (Press release, Bellicum Pharmaceuticals, DEC 7, 2020, View Source [SID1234572350]). The FDA is taking this action due to the death of a pancreatic cancer patient in the trial reported to the agency by the company. The clinical investigator and Bellicum classified the patient death as unrelated to BPX-601 and rimiducid.

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The company plans to work diligently with the FDA to address the agency’s questions and fulfill the requirements for resuming the trial. The clinical hold does not affect the company’s plans to initiate enrollment in the Phase 1/2 clinical trial of BPX-603, a dual switch GoCAR-T, in patients with HER2+ solid tumors by the end of the year.

About BPX-601

BPX-601, the company’s first GoCAR-T product candidate, incorporates iMC, Bellicum’s inducible co-activation domain. iMC (inducible MyD88/CD40) is designed to provide a powerful boost to T cell proliferation and persistence, production of immunomodulatory cytokines and enable the CAR-T to override key immune inhibitory mechanisms, including PD-1 and TGF-beta. BPX-601 is being evaluated as a treatment for pancreatic and prostate tumors expressing prostate stem cell antigen (PSCA).

On December 7, 2020 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company") reported that interim data from its ongoing Actimab-A CLAG-M Phase 1 combination trial in relapsed or refractory Acute Myeloid Leukemia (AML) were presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting (Press release, Actinium Pharmaceuticals, DEC 7, 2020, View Source [SID1234572348]).

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ASH Oral Presentation: A Phase I study of Lintuzumab Ac225 in Combination with CLAG-M Chemotherapy in Relapsed/Refractory AML

In the third and planned final dose cohort of Actimab-A CLAG-M, 100% of evaluable patients achieved remission. The trial, which is being conducted at the Medical College of Wisconsin (MCW), is advancing to a fourth dose cohort of 1.0 μCi/kg. Across the first three cohorts, 67% (10/15) patients treated with 0.25, 0.50 and 0.75 μCi/kg of Actimab-A and the standard regimen of CLAG-M achieved a Complete Remission (CR) or Complete Remission with inadequate hematopoietic recovery (CRi). Further, 83% of patients (10/12) who received 3 or fewer prior lines of treatment achieved CR or CRi. Notably, 70% of CR/CRi patients were MRD (Measurable Residual Disease) negative indicating a deep remission with no detectable disease. MRD negativity is defined as ≤0.1% AML cells. These results, which include subtherapeutic doses of Actimab-A in the first two dose cohorts, represent a marked improvement over CLAG-M treatment alone (ORR: 55%, MRD negativity: 39%) implying potential mechanistic synergy. This novel Phase 1 combination trial is for patients with relapsed or refractory acute myeloid leukemia (R/R AML) age 18 and above deemed medically fit for cytotoxic chemotherapy.

Dr. Mark Berger, Actinium’s Chief Medical Officer, said, "We look forward to continuing our work with the investigators at MCW in the Actimab-A CLAG-M combination trial. Thus far we remain thrilled with the high rates of remission, MRD negativity and transplant in this trial, which highlights the potential this combination may have for patients with R/R AML. It is exciting to see the profile of this combination emerge not only for therapeutic purposes but also for its potential as a bridge to transplant as noted by the investigators at MCW. Our CD33 program is focused on exploring the synergistic effects of Actimab-A with other therapeutic modalities and evaluating these combinations as potential backbone therapies in R/R AML."

About Actinium’s CD33 Program

Actinium’s CD33 program is evaluating the clinical utility of Actimab-A, an Antibody Radiation Conjugate (ARC) comprised of the anti-CD33 mAb lintuzumab linked to the potent alpha-emitting radioisotope Actinium-225 or Ac-225. CD33 is expressed in the majority of patients with AML and myelodysplastic syndrome, or MDS, as well as patients with multiple myeloma. The CD33 development program is driven by data from over one hundred treated patients, including a Phase 1/2 trial where Actimab-A produced a remission rate as high as 69% as a single agent. This clinical data is shaping a two-pronged approach for the CD33 program, where at low doses the Company is exploring its use for therapeutic purposes in combination with other modalities and at high doses for use for targeted conditioning prior to bone marrow transplant. Actinium currently has multiple clinical trials ongoing including the Phase 1 Actimab-A CLAG-M and Phase 1/2 Actimab-A venetoclax combination trials and is exploring additional CD33 ARC combinations with other therapeutic modalities such as chemotherapy, targeted agents or immunotherapy.