On October 4, 2021 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies and cytokines for the treatment of cancer and autoimmune diseases, reported an exclusive collaboration and worldwide license agreement with Janssen Biotech, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, to develop and commercialize plamotamab and novel XmAb B-cell targeting bispecific antibodies that are designed to conditionally activate T cells through the CD28 co-stimulatory receptor (Press release, Xencor, OCT 4, 2021, View Source [SID1234590742]). Plamotamab is a CD20 x CD3 XmAb bispecific antibody and is currently completing a Phase 1 dose-escalation study in patients with CD20-expressing hematologic malignancies.

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"The treatment landscape in B-cell lymphoma will potentially be redefined by CD20 x CD3 bispecific antibodies, such as plamotamab, and the best outcomes for patients will require creative combination approaches using complementary mechanisms of action. We are delighted to collaborate with Janssen’s leading scientists to expand the scope of the plamotamab program, particularly as we explore opportunities to combine with novel B-cell targeted CD28 bispecific antibodies that can potentially selectively enhance T-cell cytotoxic activity," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "This collaboration complements our plans to initiate combination clinical trials of plamotamab with tafasitamab and lenalidomide, and it expands our strategy to develop multiple highly active chemotherapy-free regimens for B-cell cancers."

Under the terms of the agreement, Janssen will receive worldwide exclusive development and commercialization rights to plamotamab, whether as a monotherapy or in combination regimens. Xencor will collaborate with Janssen on further clinical development of plamotamab with Janssen paying 80% and Xencor paying 20% of costs, including those for a subcutaneous formulation anticipated to enter clinical trials in 2022. In parallel, Xencor will continue, at its own expense, a previously announced clinical collaboration to evaluate the combination of plamotamab, tafasitamab and lenalidomide in patients with B-cell lymphoma, including a Phase 2 trial in relapsed or refractory diffuse large B-cell lymphoma anticipated to start in late 2021 or early 2022.

Further, Xencor will apply its XmAb bispecific Fc technology to create and characterize XmAb CD28 bispecific antibody candidates against B-cell targets during a two-year joint research collaboration, and Janssen will have an exclusive worldwide license to develop selected molecules in combination with plamotamab and other agents, such as CD3 bispecific antibodies.

Xencor will receive an upfront payment of $100 million, and Johnson & Johnson Innovation – JJDC, Inc. will purchase $25 million of newly issued shares of Xencor common stock. Xencor will be eligible to receive up to $1.188 billion in potential development, regulatory and sales milestone payments, as well as tiered royalties on net sales of products developed under the agreement, ranging from mid-teen to low-twenties percentages for products containing plamotamab and plamotamab/CD28 bispecific antibody combinations. Separate terms apply to CD28 bispecific antibodies commercialized outside of a plamotamab combination, where Xencor retains an option to co-fund development costs in exchange for higher royalties and the right to co-detail such products in the United States.

The agreement is subject to customary closing conditions, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act, and closing is expected to occur in the fourth quarter of 2021.

Conference Call

Xencor management will host a conference call today at 8:00 a.m. ET (5:00 a.m. PT) to discuss the agreement.

The live call may be accessed by dialing (877) 359-9508 for domestic callers or +1 (224) 357-2393 for international callers and referencing conference ID number 8580556. A live webcast of the conference call will be available online from the Investors section of Xencor’s website at www.xencor.com. The call will be archived on Xencor’s website for 30 days.

About Plamotamab

Plamotamab is an investigational tumor-targeted XmAb bispecific antibody that contains both a CD20 binding domain and a cytotoxic T-cell binding domain (CD3). CD20 is highly expressed across a range of B-cell tumors, including non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Engagement of CD3 by plamotamab activates T cells for highly potent and targeted killing of CD20-expressing tumor cells.

Plamotamab is currently being evaluated in a Phase 1 clinical study for the treatment of patients with CD20-expressing hematologic malignancies, including NHL and CLL. Preliminary safety and anti-tumor activity from the Phase 1 study indicated that plamotamab was generally well tolerated and demonstrated encouraging clinical activity as a monotherapy.

About XmAb CD28 Bispecific Antibodies

CD28 bispecific antibodies are a class of T cell engager designed to synergize with and complement, in a tumor-specific manner, other mechanisms of T cell activation, such as checkpoint inhibitors and CD3 bispecific antibodies. CD28 is a key immune co-stimulatory receptor on T cells that historically has proved difficult to engage therapeutically. Xencor has engineered XmAb bispecific antibodies, targeting CD28 with one binding domain and tumor cells with a second binding domain, that have demonstrated tumor-dependent T-cell activity in preclinical testing.

Xencor announced its first collaboration with Janssen to discover a CD28 bispecific antibody against an undisclosed prostate tumor target in 2020. Xencor’s lead CD28 bispecific program, XmAb808, targets B7-H3 for potential use against a wide range of tumor types and is expected to start clinical development in 2022.

On October 4, 2021 NKMax, a biotechnology company harnessing the power of the body’s immune system through the development of Natural Killer (NK) cell therapies, reported that an abstract highlighting key data from a Phase I SNK01 study in Non-Small Cell Lung Cancer (NSCLC) has been accepted for presentation at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) being held November 10 – 14, 2021, in Washington, D.C (Press release, NKMax America, OCT 4, 2021, View Source [SID1234590741]).

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Poster Presentation

Title: Phase I/IIa randomized trial evaluating safety and efficacy of SNK01 plus Pembrolizumab in patients with Stage IV Non-Small Cell Lung Cancer (NSCLC) who have failed first-line platinum-based therapy

Abstract: #1010

Poster Presentation Date and Time: November 10, 2021 from 6:00 pm – 7:00 pm EST

The poster presentation will disclose final data from the Phase I/IIa SNK01 (autologous ex-vivo activated & expanded cytotoxic NK Cells) + pembrolizumab clinical trial conducted in patients with NSCLC.

Abstracts will be available for viewing on the SITC (Free SITC Whitepaper) Annual Meeting website on November 9, 2021 at 8:00 am EST. www.sitcancer.org/2021

On October 4, 2021 AIM ImmunoTech Inc. (NYSE American: AIM) reported that it has finalized the protocol for a planned Phase 2 study of the company’s drug Ampligen as a therapy for locally advanced or metastatic late-stage pancreatic cancer (Press release, AIM ImmunoTech, OCT 4, 2021, View Source [SID1234590740]). The company expects to submit both an Investigational New Drug application (IND) and an application for Fast Track status with the U.S. Food and Drug Administration (FDA) no later than October 18, 2021.

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Amarex Clinical Research will manage the AIM-sponsored study. The Buffett Cancer Center at the University of Nebraska Medical Center (UNMC) and Erasmus MC in The Netherlands are expected to be the primary study sites, although additional sites are expected to participate.

AIM’s Pancreatic Cancer Research

The new proposed study is based on statistically significant clinical data in an early-access program where 27 subjects were treated at Erasmus MC in The Netherlands. The overall survival of the Ampligen-treated cohort was 19.2 months from the start of FOLFIRINOX, compared to 12.5 months in the historical control group. This increase of 6.7 months in the Ampligen-treated group was clinically and statistically significant. Additionally, several subjects are still alive more than three years later. These detailed data were filed with and supported the recent approval of orphan drug status for Ampligen by both the FDA and the European Medicines Agency. These detailed data will also be a component of the upcoming Phase 2 IND submission and a justification for the Fast Track application.

Prof. C.H.J. van Eijck, MD, PhD, and his team at Erasmus MC intend to publish a detailed clinical report on their results in a peer-reviewed journal no later than January 2022. AIM will publicly release the detailed data and analysis at that time.

Overview of the Planned AMP-270 Study

The planned AMP-270 clinical trial will be a Phase 2, randomized, open-label, controlled, parallel-arm study with the primary objective of comparing the efficacy of Ampligen when added to SOC (standard of care) versus SOC alone for subjects with advanced pancreatic carcinoma recently treated with FOLFIRINOX chemotherapy regimen. Secondary objectives include comparing safety and tolerability. There will be two parallel arms and approximately 250 eligible subjects will be randomized 1:1 to receive either 1) Ampligen alone or Ampligen combined with SOC, or 2) SOC alone.

The parallel control arm will receive SOC without Ampligen. This will consist of monitoring for disease progression along with active anticancer therapy as determined by the patients’ physicians.
Patients in the Ampligen-plus-SOC arm will be administered twice weekly Ampligen intravenous (IV) infusions. Subjects will be monitored for disease progression and may also receive anticancer SOC therapy (depending on their treating physicians).
Amarex CEO Kazem Kazempour, PhD, states: "The Phase 2 study design includes an interim data analysis intended to allow for the transition from a Phase 2 to a Phase 3 study pending the FDA’s review and approval. The interim data may also allow for a "Breakthrough" drug designation from the FDA, which provides significant advantages to the clinical development program."

Pancreatic Cancer Subject-Matter Experts Discuss the New Study

Prof. Kelsey Klute, MD, of the Buffett Cancer Center at UNMC, and the study’s principal investigator in the United States, states: "Most people diagnosed with pancreatic cancer don’t survive more than a year after their diagnosis. There is a critical need for more effective therapies to treat this lethal disease. Based on the Erasmus data and our preclinical data, we’re optimistic about the activity of Ampligen in treating pancreatic cancer. We’ve designed this clinical trial to test whether Ampligen improves survival compared to the current standard of care. But I think it’s equally important that this study will also help us understand the effect of Ampligen at the cellular level of the tumor and the immune system – to learn why and how it works in certain patients and why it might fail in others – and set the stage to refine the use of Ampligen in the future."

Prof. Michael A. "Tony" Hollingsworth, PhD, also of UNMC, a world-renowned pancreatic cancer researcher who is designing exploratory experimental endpoints to supplement the survival-based primary endpoint, states: "We have designed correlative studies to test the hypothesis that administration of Ampligen in the maintenance setting will improve survival by enhancing tumor-specific immunity and also systemic immunity to opportunistic pathogens that contribute to the patients demise during end stage disease."

Prof. C.H.J. van Eijck, MD, PhD, states: "The overall survival of the experimental group was compared to a well matched historical control cohort matched for age, gender, stage of disease, and number of cycles of FOLFIRINOX chemotherapy. Median survival was significantly higher in the Ampligen arm as compared to the historical controls. Based on these data, I see the potential for Ampligen as a meaningful extension of the standard of care for advanced pancreatic cancer, which we are planning to investigate further in the upcoming randomized control trial."

On October 4, 2021 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported details about its plan to initiate a randomized Phase 2 clinical study evaluating SRF388, a potential first-in-class antibody against IL-27, in combination with Roche’s atezolizumab and bevacizumab, in patients with treatment-naïve hepatocellular carcinoma (HCC) (Press release, Surface Oncology, OCT 4, 2021, View Source [SID1234590735]). Initiation-enabling activities are underway, and the Company expects to dose the first patient in early 2022.

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"We are delighted to announce this new study of SRF388 in HCC, which offers the potential for increased clinical benefit to patients and broadens Surface’s clinical program for our potential first-in-class IL-27 antibody," said Alison O’Neill, M.D., chief medical officer. "We believe there is strong scientific rationale for targeting the immunosuppressive cytokine IL-27 as a first-line treatment for this patient population, especially in conjunction with PD-1 and VEG-F blockade, which has proven clinical efficacy in extending survival and progression-free survival (PFS) based on the IMBrave150 study versus sorafenib. We believe that our randomized Phase 2 approach is well suited to provide robust data for these patients."

The blinded, randomized Phase 2 study is expected to enroll approximately 100 first-line patients with unresectable or metastatic HCC. Patients will be randomized to receive either SRF388 or a placebo in combination with atezolizumab and bevacizumab. The study will primarily evaluate investigator-assessed PFS of SRF388 in combination with atezolizumab and bevacizumab compared to atezolizumab and bevacizumab. Secondary endpoints from the trial will include safety, overall response rates and duration of response. Because this is a blinded study, Surface does not expect to have detailed clinical data prior to study conclusion, but does anticipate a futility analysis in early 2023 and final data in the first half of 2024.

Initial data presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting earlier this year showed SRF388 was well tolerated at all doses tested, set the recommended Phase 2 dose at 10 mg/kg every four weeks and demonstrated evidence of monotherapy activity.

Financial Outlook:
Surface has expanded its existing debt facility with K2 HealthVentures, increasing the capacity to $50M. Based upon its current operating plan, including the SRF388 first-line HCC randomized Phase 2 clinical study, which includes the extended debt facility, Surface maintains a projected cash runway through 2023.

On October 4, 2021 Selecta Biosciences, Inc. (NASDAQ: SELB), a biotechnology company leveraging its clinically validated ImmTOR platform to develop tolerogenic therapies that selectively mitigate unwanted immune responses, reported that it has entered into a strategic licensing agreement with Takeda Pharmaceutical Company Limited ("Takeda") to develop targeted, next-generation gene therapies for two indications within the field of lysosomal storage disorders (Press release, Selecta Biosciences, OCT 4, 2021, View Source [SID1234590734]). The collaboration leverages Selecta’s ImmTOR platform to enable redosing of transformative therapies.

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Carsten Brunn, Ph.D., president and chief executive officer of Selecta, added, "Takeda is an ideal partner to maximize the potential of our ImmTOR platform in gene therapy. Their extensive capabilities as a global biopharmaceutical leader and expertise in rare diseases gives us a high degree of confidence that Selecta’s vision will be realized. Together, we look forward to overcoming barriers to current efforts in AAV-driven gene therapy, as well as striving to address immunogenicity constraints and unmet patient needs. This collaboration provides additional validation and further demonstrates the robust value of our ImmTOR platform, which may enable redosing of potentially life-saving gene therapies. We are excited to expand our growing pipeline with Takeda and build on the momentum of our rapidly advancing proprietary gene therapy programs."

Under the terms of the agreement, Selecta is entitled to receive an undisclosed upfront payment and up to $1.124 billion in future additional payments over the course of the partnership that are contingent on the achievement of development or commercial milestones or Takeda’s election to continue its activities at specified development stages. Selecta is also eligible for tiered royalties on future commercial sales.

"Partnerships are critical as we look to build differentiated gene therapy programs where we have the opportunity to combine novel platform technologies that each aim to solve the challenges associated with first-generation gene therapies," said Madhu Natarajan, head of Takeda’s rare diseases drug discovery unit. "Selecta’s ImmTOR platform is designed to mitigate unwanted immune responses allowing for redosing, which could have broad applicability across our gene therapy programs for a range of diseases."