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.

On December 7, 2020 Pfizer Inc. (NYSE:PFE) reported safety and clinical response results from the ongoing Phase 1 study (NCT03269136) for PF-06863135, an investigational B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody (Press release, Pfizer, DEC 7, 2020, View Source [SID1234572364]). Data from 30 patients with relapsed or refractory multiple myeloma showed manageable safety across all subcutaneous dose levels with no dose-limiting toxicities observed, and 83% of patients achieved a clinical response at the highest dose level. The results will be presented today at the Virtual American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

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"Despite treatment advances, multiple myeloma remains incurable and there is a substantial need for breakthroughs for patients," said Jeff Settleman, Senior Vice President & Chief Scientific Officer, Oncology R&D, Pfizer. "The very high response rate observed with PF-06863135, coupled with manageable safety and the convenience of subcutaneous administration, underscores the potential impact this medicine may have for people living with this devastating disease. These findings support continued development of PF-06863135 for people with multiple myeloma, both as monotherapy and in combination with standard or novel therapies."

PF-06863135 is a bispecific antibody designed to bind to BCMA which is highly expressed on the surface of multiple myeloma cells, and the CD3 receptor found on the surface of cancer-fighting T cells, bridging them together to activate an immune response. Binding affinity to BCMA and CD3 has been optimized, enabling more potent T-cell-mediated anti-myeloma activity. Subcutaneous administration of PF-06863135 is intended to allow higher doses than intravenous administration without increasing adverse events.

The primary objectives of this portion of the study were to assess safety and tolerability of PF-06863135 administered subcutaneously, to determine the maximum tolerated dose, and to select the recommended Phase 2 dose. In the study, no dose-limiting toxicities were observed across any of the subcutaneous dose levels evaluated (80 to 1,000 μg/kg weekly) during dose escalation. Cytokine release syndrome (CRS) was reported in 73.3% of patients and was limited exclusively to grade 1 (56.7%) or grade 2 (16.7%). Grade 3 or higher adverse events (AEs) occurring in more than 10% of patients included lymphopenia (53.3%), neutropenia (26.7%), thrombocytopenia (16.7%) and anemia (16.7%).

The overall response rate (ORR) was 80% among the 20 patients treated in cohorts across the efficacious dose range of 215 to 1,000 μg/kg weekly. Among these 20 patients, six achieved stringent complete response or complete response, three achieved very good partial response, and six achieved partial response. Three responding patients had received at least one prior BCMA-targeted therapy. At the highest dose level of 1,000 μg/kg, the ORR was 83% (5/6 patients). Based on these data, 1,000 μg/kg weekly is the recommended Phase 2 dose.

About the PF-06863135 Phase 1 Trial

NCT03269136 is a Phase 1, open-label, multi-dose, multicenter, dose escalation, safety, pharmacokinetic (PK) and pharmacodynamic study of PF-06863135 for adult patients with advanced multiple myeloma who have relapsed after, or are refractory to, standard therapies. Part 1 of this two-part study assessed the safety and tolerability of increasing dose levels of PF-06863135. The study enrolled 80 patients and evaluates PF-06863135 administered intravenously or subcutaneously. Preliminary results for intravenous administration were reported at ASH (Free ASH Whitepaper) in 2019.1 For more information about the trial, visit www.clinicaltrials.gov.

About Multiple Myeloma

Multiple myeloma is a blood cancer that affects plasma cells made in the bone marrow. Healthy plasma cells make antibodies that help the body fight infection. According to the latest figures available, there are approximately 32,270 new cases of multiple myeloma diagnosed annually in the United States and 160,000 globally.2,3 Despite treatment advances, multiple myeloma remains incurable. The median survival is just over 5 years, and most patients receive four or more lines of therapy.4

On December 7, 2020 Sutro Biopharma, Inc. (Nasdaq: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation cancer and autoimmune therapeutics, reported a proposed underwritten public offering in which it intends to offer and sell 5,000,000 shares of its common stock (Press release, Sutro Biopharma, DEC 7, 2020, View Source [SID1234572382]). In addition, Sutro intends to grant the underwriters a 30-day option to purchase up to an additional 750,000 shares of common stock offered in the public offering. All of the shares of common stock are being offered by Sutro. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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Cowen, Piper Sandler and Wells Fargo Securities are acting as joint book-running managers in the offering. Wedbush PacGrow and JMP Securities are acting as co-managers for the offering.

Sutro intends to use the net proceeds from the proposed offering, together with its existing cash, cash equivalents and marketable securities, to fund the continued clinical development of STRO-001 and STRO-002 and the remainder to fund the further development of its technology platform, including manufacturing, to broaden its pipeline of product candidates, and for working capital and general corporate purposes.

The shares are being offered by Sutro pursuant to a registration statement on Form S-3 previously filed and declared effective by the Securities and Exchange Commission (SEC). A preliminary prospectus supplement and accompanying prospectus relating to this offering will be filed with the SEC. When available, copies of the preliminary prospectus supplement and the accompanying prospectus relating to this offering may be obtained from: Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, Attn: Prospectus Department, by telephone at (833) 297-2926, or by email at [email protected]; Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, Minnesota 55402, by telephone at (800) 747-3924, or by email at [email protected]; or Wells Fargo Securities, LLC, Attention: Equity Syndicate Department, 500 West 33rd Street, New York, New York 10001, by telephone at (800) 326-5897, or by email at [email protected]. Electronic copies of the preliminary prospectus supplement and accompanying prospectus will also be available on the website of the SEC at View Source

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any securities of Sutro, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On December 7, 2020 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported positive interim Phase 1 data on HB-201, its replicating monotherapy for the treatment of HPV16+ cancers (Press release, Hookipa Pharma, DEC 7, 2020, View Source [SID1234572314]). The results are from the initial dose escalation cohorts of an ongoing Phase 1/2 clinical trial (NCT04180215) evaluating HB- 201 as therapy for patients with advanced HPV16+ metastatic cancers. HOOKIPA will host a conference call and live audio webcast today at 8:30am EST.

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These interim data support proof of concept for HB-201 monotherapy as a new immunotherapy for a difficult-to-treat patient population with multiple prior treatment failures. As of December 4, 2020, 22 patients have been enrolled in the first two cohorts, of which 15 were eligible for evaluation. Among the 15 evaluable patients, 11 patients had relapsed/refractory metastatic squamous cell head and neck cancer (HNSCC), all of whom had progressed on prior therapy with a PD1 inhibitor. As per RECIST1.1, in patients with third-line or later HNSCC, HB-201 demonstrated an unconfirmed response rate of 18% (one unconfirmed complete responder and one unconfirmed partial responder) and a 73% disease control rate (six stable disease patients, in addition to the two unconfirmed responses referenced above).

Median progression-free survival (mPFS) is currently measured at 72 days and is ongoing. Although not demonstrated in a head-to-head trial, these HB-201 results, in more heavily treated patients who progressed on a PD1 inhibitor, compare favorably to the benchmark data of a 13% overall response rate and a 60-day mPFS1 for nivolumab in second-line PD1 inhibitor naïve HNSCC patients, based on data published from the third-party registrational study.

Encouraging efficacy signals were also seen in the more heterogeneous group of all 15 evaluable patients with HPV16+ cancers treated in this trial, comprised of the 11 HNSCC patients summarized above and four other patients with HPV16+ cervical, anal, or vaginal tumors. In these 15 patients, HB-201 demonstrated an unconfirmed response rate of 13%, a disease control rate of 67%, and a median PFS that is also ongoing and currently measured at 72 days.

"We are thrilled by these preliminary HB-201 data, as they show the potential of our arenavirus platform in oncology and represent future possible therapeutic options for patients with HPV16+ cancers," said Joern Aldag, Chief Executive Officer of HOOKIPA. "The early response with our single-vector HB-201 therapy highlights the potential of our replicating technology, especially as we explore alternating two-vector therapy with HB-201/HB-202, and a future combination with a PD-1 inhibitor, both of which we hope will deliver even greater responses."

Of the 22 patients enrolled on the trial as of December 4th, preliminary safety data show that HB-201 has been well tolerated. Treatment-related adverse events were reported by 41% of participants. Almost all reported events were Grade 1 and 2 and included fatigue, fever, decreased appetite, constipation, nausea, and itching. Only one serious adverse event deemed related to HB-201, Grade 3 fatigue leading to hospitalization, has been reported to date. The rate of adverse events was consistent regardless of administration route.

"There remains a considerable unmet need in the treatment of HPV16+ cancers, particularly those in head and neck, and these preliminary data on HB-201 as a monotherapy are encouraging," said Alan L. Ho, MD, PhD, a medical oncologist at Memorial Sloan Kettering Cancer Center and an investigator on the trial.

About the trial
This Phase 1/2 clinical trial is an open-label dose-escalation and dose-expansion trial in individuals with treatment-refractory HPV16+ cancers. The primary endpoint of the Phase 1 trial is a recommended Phase 2 dose based on safety and tolerability. Secondary endpoints include anti-tumor activity as defined by RECIST 1.1, immunogenicity, safety, and tolerability.

The trial is designed to evaluate different dose levels of HB-201 as a single-vector therapy, as an alternating two-vector therapy together with HB-202, and in combination with a PD-1 inhibitor. Dosing frequencies of every three weeks and every two weeks are being explored during dose escalation.

Since the trial opened in December 2019, 22 patients with metastatic HPV16+ tumors have been enrolled in the HB-201 monotherapy segment: 17 with squamous cell head and neck tumors, two with cervical, one with nasopharyngeal, one with anal, and one with vaginal. Patients had received at least two prior therapies, and most patients progressed on a PD-1 inhibitor, a platinum-containing regimen or both. Enrollment is ongoing and HOOKIPA expects to share additional interim clinical data from the HB-201/HB-202 alternating two-vector therapy segment in mid-2021.

About HB-201/HB-202
HB-201 and HB-202 are engineered using HOOKIPA’s replicating arenaviral vector platform. They are designed to use different arenavirus backbones (LCMV for HB- 201 and PICV for HB-202), while expressing the same antigen, an E7/E6 fusion protein derived from HPV16. In pre-clinical studies, alternating administration of HB-202 and HB-201 resulted in a ten-fold increase in immune response and better disease control than either compound alone.

Conference call
HOOKIPA will host a conference call and live audio webcast today at 8:30am EST to discuss the HB-201 monotherapy data from the interim analysis of the Phase 1 trial. To access the conference call, please dial +1 877 870 9135 (from the US) or +44 2071 928338 (international) and refer to conference ID 9747865. The webcast and the presentation will be available within the Investors & Media section of HOOKIPA’s website at View Source An archived replay will be accessible for 30 days following the event.

About Human Papillomavirus
Human Papillomavirus, or HPV, is estimated to cause about 5 percent of the worldwide burden of cancers. This includes approximately 99 percent of cases in cervical, up to 60 percent of head and neck, 70 percent of vaginal and 88 percent of anal cancers.

The majority of these cancers are caused by the HPV serotype 16. Most infections with HPV are cleared from the body with no lasting consequences. However, in some cases, HPV DNA becomes integrated into chromosomal DNA. When host cells take up this DNA, they express the HPV E6 and E7 proteins. This uptake can potentially lead to cancer since expression of these proteins leads to alterations in cell cycle control, which in turn predisposes these cells to become cancerous.

On December 7, 2020 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer and autoimmune diseases, reported it has entered into a research collaboration and license agreement with Janssen Biotech, Inc. (Janssen) (Press release, Xencor, DEC 7, 2020, View Source [SID1234572333]). The research and license agreement is focused on the discovery of XmAb bispecific antibodies against CD28, an immune co-stimulatory receptor on T cells, and an undisclosed prostate tumor target, for the potential treatment of patients with prostate cancer. Additionally, Xencor has a right to access select, predefined agents from Janssen’s portfolio of clinical-stage drug candidates and commercialized medicines to evaluate potential combination therapies in prostate cancer with agents in its own pipeline in non-registrational clinical studies. Janssen has the same right with Xencor’s portfolio of clinical-stage drug candidates to evaluate potential combination therapies in prostate cancer, as well.

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"Our XmAb bispecific Fc domains enable the creation of a wide range of multi-specific antibody and protein structures, such as bispecific antibodies in our new CD28 platform. These antibodies can co-stimulate T cells in a tumor-target dependent manner and can synergize with both checkpoint inhibitor therapies and other tumor-targeted agents, like CD3 bispecific antibodies, in order to enhance anti-tumor activity," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "In addition, the ability to study combinations of therapies from both companies’ prostate cancer portfolios leverages Xencor’s broad clinical pipeline and the leading prostate cancer therapeutics portfolio at Janssen. This collaboration with Janssen expands the use of our CD28 platform and complements our first wholly owned internal candidate, a B7-H3 x CD28 bispecific antibody designed to treat a range of solid tumors, which is currently advancing through preclinical development."

Under the terms of the agreement, Xencor will apply its XmAb bispecific Fc technology to create and characterize XmAb CD28 bispecific antibody candidates against the tumor target specified by Janssen. Preclinical activities and all clinical development, regulatory and commercial activities will be conducted by Janssen, which has exclusive worldwide rights to develop and commercialize the novel drug candidates. Xencor will receive an upfront payment of $50 million and will be eligible to receive development, regulatory and sales milestone payments and high-single digit to low-double digit percent royalties on net sales.

Upon clinical proof of concept for a bispecific antibody candidate, Xencor has the right to opt-in to fund 20 percent of development costs and to perform up to 30 percent of the detailing efforts in the United States; Xencor would be eligible for milestone payments and low-double digit to mid-teen percent royalties on net sales.

The agreement is subject to customary closing conditions, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act, and closing is expected to occur by year end.