On November 12, 2021 Oncorus, Inc. (Nasdaq: ONCR), a viral immunotherapy company focused on driving innovation to transform outcomes for cancer patients, reported that initial safety, tolerability and immune activation and clinical response data from its ongoing Phase 1 open-label, multi-center, dose escalation and expansion clinical trial of ONCR-177 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting, taking place November 12-14th in Washington, D.C. and virtually (Press release, Oncorus, NOV 12, 2021, View Source [SID1234595342]). In the fully enrolled and completed surface lesion dose escalation part of the Phase 1 study, ONCR-177 was well tolerated with no dose-limiting toxicities. In addition, three of eight evaluable patients at RP2D (as of a November 8, 2021 data cut-off) with cutaneous melanoma, squamous cell carcinoma of the head and neck (SCCHN), and mucosal melanoma, experienced clinical benefit after two doses of ONCR-177. ONCR-177, Oncorus’ lead oncolytic HSV product candidate, is an intratumorally (iTu) administered viral immunotherapy being developed for multiple solid tumor indications.

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"I’m encouraged by the findings from the ONCR-177 Phase 1 trial we presented at SITC (Free SITC Whitepaper) today," said Jong Chul Park, M.D., Instructor, Harvard Medical School and Assistant in Medicine, Massachusetts General Hospital, and first author on the SITC (Free SITC Whitepaper) abstract. "We are evaluating ONCR-177 in heavily pretreated cancer patients with advanced disease and no available standard of care. I’m impressed by the overall favorable safety and tolerability profile of ONCR-177 observed to date and the clinical responses demonstrated in some patients after only four weeks of monotherapy treatment. I look forward to enrolling patients in the combination cohort with pembrolizumab with the potential for amplification of clinical benefit."

Oncorus has engineered its proprietary HSV platform to develop improved iTu-administered viral immunotherapies that have the potential to enhance potency without sacrificing safety, a challenge that has been encountered by earlier-generation programs in this class. ONCR-177 incorporates two innovative, orthogonal safety strategies — the use of microRNA target sequences and a proprietary mutation engineered in an HSV-1 protein known as UL37 — to allow for replication only in tumors (Kennedy, Mol Thera Onco, 2020). These innovations allow for ONCR-177 to keep its ability to resist interferon challenge, via the retention of γ34.5, which is deleted in other HSV-based viral immunotherapies either on the market or in development today, and to be armed with five immunomodulatory transgenes: IL-12, FLT3L, CCL4, and antagonists of clinically proven immune checkpoints PD-1 and CTLA-4.

Theodore (Ted) Ashburn, M.D., Ph.D., President and CEO of Oncorus, commented, "We are excited by these data as they provide strong proof of concept for our HSV platform. To see clinical benefit in heavily pretreated patients across multiple histologies is a testament to the promise of our platform, of ONCR-177, and of our ability to deliver a potent, multidimensional attack on cancer without sacrificing safety, thanks to our novel engineering. Furthermore, these data also support the development of ONCR-GBM, our HSV preclinical candidate being developed to specifically treat brain tumors, including glioblastoma multiforme, as well as potential future HSV programs. With several important milestones slated for 2022, we look forward to continuing to provide updates on ONCR-177 and the rest of our pipeline."

ONCR-177 Phase 1 Trial Design

The Phase 1 clinical trial is designed to evaluate the safety, tolerability and initial efficacy of ONCR-177 administered alone and in combination with Merck’s anti-PD-1 therapy, KEYTRUDA, in patients with advanced and/or refractory cutaneous, subcutaneous or metastatic nodal solid tumors or with liver metastases of solid tumors. The trial is composed of four primary parts:

Part 1: surface lesion dose escalation (to determine RP2D) and tissue-specific dose expansion monotherapy, including breast cancer, melanoma, non-melanoma skin cancer, and head and neck cancer expansion cohorts;
Part 2: surface lesion dose expansion combination with KEYTRUDA;
Part 3: visceral injection into liver metastases dose escalation (to determine RP2D) and dose expansion monotherapy; and
Part 4: visceral injection dose expansion combination therapy with pembrolizumab.
Key safety and exploratory biomarkers include ONCR-177 detection in skin swabs, anti-HSV-1 antibodies, ONCR-177 payloads in blood, peripheral inflammatory cytokines, immune infiltration of the tumor and PD-L1 immunohistochemistry, or IHC, expression.

Phase 1 Initial Safety and Efficacy Results

Today, Oncorus presented preliminary findings at SITC (Free SITC Whitepaper) from Part 1 of the trial, including the fully enrolled and completed dose escalation cohorts (n=14) and patients enrolled in the dose expansion monotherapy as of a November 1, 2021 data cut-off (n=5).

ONCR-177 administered to heavily pretreated patients with advanced, injectable solid tumors was well-tolerated with no dose-limiting toxicities, and the recommended RP2D was determined to be 4×108 PFU in 4 mL. No treatment-related adverse events exceeded Grade 3, and the most common Grade 1 and 2 adverse events were fatigue, chills, nausea, and mild, dose-dependent cytokine release syndrome, or CRS. No infectious virions were detected in skin swabs, in line with ONCR-177 safety expectations.

Seven heavily pretreated patients have been enrolled to date in the ongoing surface lesion, histology-specific monotherapy expansion cohorts. As of November 1, four of these expansion patients were evaluable at the time of the SITC (Free SITC Whitepaper) poster presentation; one patient went off study after a single dose and is not evaluable; two are too early in their treatment course to be evaluable. The four evaluable monotherapy expansion patients are in addition to four evaluable monotherapy escalation patients treated at the RP2D. After four weeks of ONCR-177 monotherapy treatment (two doses) at RP2D, three of these eight evaluable patients (all in the surface lesion monotherapy expansion cohorts) demonstrated clinical benefit as follows:

Partial response in a patient with cutaneous melanoma as measured by calipers per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (surface tumor not measurable by CT scan)
Investigator-reported clinical response in a squamous cell carcinoma of the head and neck (SCCHN) patient in injected lymph node after four weeks
Stable disease in a patient with mucosal melanoma as measured by RECIST 1.1 with improvement in cancer-related symptoms
Several findings from the study thus far suggest immune stimulation of the tumor microenvironment, including mild, dose-dependent CRS in association with increased interferon-γ (IFN-γ) and T cell proliferation in blood, as well evidence of tumor PD-L1 expression and immune cell infiltration.

Oncorus plans to initiate enrollment in the surface lesion dose combination expansion (Part 2) and the visceral lesion dose monotherapy escalation (Part 3) by the end of 2021. The company plans to report additional surface lesion monotherapy expansion data in mid-2022, and initial surface lesion combination expansion data (ONCR-177 + KEYTRUDA) and visceral lesion monotherapy dose escalation data in late 2022.

For more information on the ongoing Phase 1 study, please visit: View Source

Conference Call and Webcast Information
Oncorus will host a conference call and live webcast with slides and Q&A today at 8:30 a.m. ET. Igor Puzanov, M.D., MSCI, FACP, who serves as Director of Center for Early Phase Clinical Trials, Senior Vice President of Clinical Investigation, and Chief of the Melanoma Section, at the Roswell Park Comprehensive Cancer Center in Buffalo, New York, will join Oncorus management for the call. Dr. Puzanov is also participating as an investigator in the ONCR-177 Phase 1 clinical trial.

To participate in the conference call, please dial (833) 614-1530 (domestic) or (520) 809-9930 (international) and refer to conference ID 8556488. A live webcast of the presentation will be available at View Source A replay of the webcast will be available shortly after the conclusion of the call and archived on the company’s website for 30 days following the call.

On November 12, 2021 Bio-Path Holdings, Inc., (NASDAQ:BPTH), a biotechnology company leveraging its proprietary DNAbilize liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid cancer drugs, reported its financial results for the third quarter ended September 30, 2021 and provided an update on recent corporate developments (Press release, Bio-Path Holdings, NOV 12, 2021, View Source [SID1234595382]).

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"The clinical and regulatory advances made during the third quarter position us to initiate two key trials with prexigebersen-A in solid tumors and BP1002 in relapsed/refractory acute myeloid leukemia (AML) patients," stated Peter Nielsen, President and Chief Executive Officer of Bio-Path Holdings. "Looking to the balance of the year, we look forward to presenting safety and preliminary efficacy data from our ongoing Phase 2 trial of prexigebersen for the treatment of AML before an audience of world-leading oncologists at the American Society for Hematology Annual Meeting. Collectively, the progress we are making throughout 2021 is bringing us one step closer to achieving our goal of bringing new medicines to the fight against cancer."

Recent Corporate Highlights

Clearance of IND Application for Phase 1/1b Clinical Trial of Prexigebersen-A. In October, Bio-Path announced that the U.S. Food and Drug Administration (FDA) had reviewed and cleared the Investigational New Drug (IND) application to initiate a Phase 1/1b clinical trial of prexigebersen-A (liposomal Grb2-A or BP1001-A) in patients with solid tumors, including ovarian, endometrial, pancreatic and triple negative breast cancer. Prexigebersen-A is a modified drug product with the same drug substance as prexigebersen but includes formulation enhancements to produce smaller drug nanoparticles.

Clearance of IND Application for BP1002. In August, the Company announced that the FDA had reviewed and cleared the IND application for BP1002 (liposomal Bcl-2), the Company’s second drug candidate, for an initial Phase 1/1b clinical trial that will evaluate the ability of BP1002 to treat refractory/relapsed AML patients.
Financial Results for the Third Quarter Ended September 30, 2021

The Company reported a net loss of $2.1 million, or $0.29 per share, for the three months ended September 30, 2021, compared to a net loss of $3.0 million, or $0.80 per share, for the three months ended September 30, 2020.

Research and development expense for the three months ended September 30, 2021 decreased to $1.0 million, compared to $2.0 million for the three months ended September 30, 2020, primarily due to timing of activities related to our clinical trial for prexigebersen in AML and timing of drug material manufacturing and shipping activities.

General and administrative expense for the three months ended September 30, 2021 increased to $1.1 million, compared to $1.0 million for the three months ended September 30, 2020, primarily due to increased stock-based compensation expense.

As of September 30, 2021, the Company had cash of $26.6 million, compared to $13.8 million at December 31, 2020. Net cash used in operating activities for the nine months ended September 30, 2021 was $7.1 million, compared to $8.4 million for the comparable period in 2020. Net cash provided by financing activities for the nine months ended September 30, 2021 was $20.0 million.
Conference Call and Webcast Information

Bio-Path Holdings will host a conference call and webcast today at 8:30 a.m. ET to review these third quarter 2021 financial results and to provide a general update on the Company. To access the conference call please dial (844) 815-4963 (domestic) or (210) 229-8838 (international) and refer to the conference ID 6684508. A live audio webcast of the call and the archived webcast will be available in the Media section of the Company’s website at www.biopathholdings.com.

On November 12, 2021 aTyr Pharma, Inc. (Nasdaq: LIFE), a biotherapeutics company engaged in the discovery and development of innovative medicines based on novel biological pathways, reported that Sanjay S. Shukla, M.D., M.S., President and Chief Executive Officer, will present at two upcoming virtual investor conferences in November (Press release, aTyr Pharma, NOV 12, 2021, View Source [SID1234595452]).

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Details of the events are as follows:

Conference: Stifel 2021 Virtual Healthcare Conference
Date: Wednesday, November 17, 2021
Time: Live Corporate Presentation at 4:40pm EST / 1:40pm PST

Conference: Piper Sandler 33rd Annual Virtual Healthcare Conference
Date: Monday, November 22, 2021
Time: Pre-recorded Fireside Chat available on demand starting at 10:00am EST / 7:00am PST

In addition to the presentations, company management will be available to participate in virtual one-on-one meetings with investors who are registered attendees of the conferences. Following the events, a replay of each presentation will be available on the Investor’s section of the company’s website at www.atyrpharma.com.

On November 12, 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 the presentation of new data from multiple preclinical XmAb bispecific antibody programs and its preclinical IL-12-Fc cytokine program, XmAb662, at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Xencor, NOV 12, 2021, View Source [SID1234595469]).

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"XmAb bispecific Fc domains enable the rapid design and simplified development of a wide range of multi-specific antibodies and other protein structures, such as engineered cytokines. At SITC (Free SITC Whitepaper), we are presenting new data from multiple preclinical programs, including our first presentation of XmAb NK cell engagers, an exciting modality that mechanistically synergizes with our investigational engineered cytokine candidates," said John Desjarlais, Ph.D., senior vice president and chief scientific officer at Xencor. "Our preclinical programs show the power of Xencor’s platform to create exciting XmAb drug candidates that access new biologies and continually supply our clinical pipeline with differentiated molecules."

The posters will be archived under "Events & Presentations" in the Investors section of the Company’s website located at www.xencor.com.

Abstract 707, "IL12 Fc-fusions engineered for reduced potency and extended half-life exhibit strong anti-tumor activity and improved therapeutic index compared to wild-type IL12 agents"

IL-12 is a potent pro-inflammatory cytokine that promotes high levels of interferon gamma secretion from T-cells and NK cells, increasing their cytotoxicity and the immunogenicity of the tumor microenvironment by making tumor antigens more visible to the immune system. Prior clinical studies have demonstrated IL-12 has significant anti-tumor activity; however, its toxicity has limited its potential. Xencor’s IL-12 program follows the same potency reduction design strategy as the Company’s IL15-Fc fusions in oncology, where reduced potency led to improved pharmacokinetics, pharmacodynamics and safety in preclinical studies. In addition, preliminary clinical data from Xencor’s IL15-Fc program, XmAb306, showed generally good tolerability and robust and sustained immune cell expansion.

IL12-Fc fusions were engineered with reduced potency in order to improve potential tolerability, slow receptor-mediated clearance and prolong half-life in vivo, compared to native IL-12. These potency-reduced IL12-Fc fusions demonstrated significant anti-tumor activity in vivo, concurrent with activation and proliferation of CD8+ T cells and with interferon gamma production.

The addition of Xencor’s half-life extending Xtend Fc mutations further improved exposure of the molecules over time. In non-human primates, the engineered cytokines had an improved pharmacokinetic profile and therapeutic window compared to a native cytokine-Fc fusion, with superior exposure, a more gradual dose response and similar levels of cytokine production in serum.

XmAb662 was selected for further development and demonstrated significant anti-tumor activity in vivo, concurrent with increases in NK cells, T cells, serum IP10 and serum interferon gamma, which were further enhanced when combined with an anti-PD-1 antibody. The Company anticipates submitting an IND application for XmAb662 in 2022.

Abstract 698, "PDL1-targeted CD28 costimulatory bispecific antibodies enhance T cell activation in solid tumors"

T cells in the tumor microenvironment require both T cell receptor (TCR) and co-stimulatory receptor engagement to achieve full activation. CD28 is a key immune co-stimulatory receptor on T cells; however, the ligands that activate T cells through CD28 are usually not expressed on tumor cells. Targeted CD28 bispecific antibodies, a new class of T cell engager, may provide conditional co-stimulation of T cells, for example, to T cells recognizing neoantigens or in concert with CD3 T-cell engaging bispecific antibodies.

Xencor engineered PD-L1 x CD28 bispecific antibodies to provide conditional co-stimulation of T cells, activating them when bound to PD-L1+ cells. PD-L1, which is expressed on many types of tumors, suppresses anti-tumor responses by the immune system and can inhibit CD28 by engaging PD-1. A PD-L1 x CD28 bispecific antibody, therefore, may promote CD28 co-stimulation and simultaneously block CD28’s suppression by PD-1.

In vitro, the combination of the PD-L1 x CD28 and a CD3 T cell engager enhanced T cell activation and proliferation compared to the CD3 bispecific alone. PD-L1 x CD28 also enhanced the interaction between T cells and antigen presenting cells and exhibited strong CD28-dependent anti-tumor activity in mice. PD-L1 x CD28 was well tolerated in non-human primates and exhibited favorable pharmacokinetics. Modeling and preclinical data suggest a dosing schedule consistent with typical checkpoint inhibitor regimens.

Abstract 872, "PD1 x TGFβR2 and CD5 x TGFβR2 bispecifics selectively block TGFβR2 on target-positive T cells, promote T cell activation, and elicit an anti-tumor response in solid tumors"

TGFβ is an inhibitory cytokine, and its production in solid tumors is a significant mechanism used by tumors to avoid recognition by the immune system. While TGFβ inhibition is expected to promote an anti-tumor response, systemic blockade of TGFβ has also been associated with toxicity.

Xencor engineered two XmAb bispecific antibodies, PD-1 x TGFβR2 and CD5 x TGFβR2, to selectively block the suppressive activity of TGFβ on specific T-cell populations and to enhance their anti-tumor activity while avoiding the toxicity associated with systemic blockade. PD-1 and CD5 were selected to direct TGFβ blockade to activated or all T cells, respectively.

In vitro, both bispecific antibodies exhibited highly selective blocking of TGFβ activity in PD-1-high and CD5-positive T cell populations. PD-1 x TGFβR2 and CD5 x TGFβR2 were active in vivo and promoted T cell engraftment and anti-tumor response. Anti-tumor activity was significantly enhanced when combined with an anti-PD-1 antibody, compared to either anti-PD-1 or the bispecific antibody alone.

Abstract 787, "Natural killer cell engagers activate innate and adaptive immunity and show synergy with proinflammatory cytokines"

Xencor’s XmAb natural killer cell engagers (NKEs) are multifunctional antibodies that target multiple activating receptors on the surface of NK cells and bind to tumor associated antigens.

Xencor engineered a B7-H3 x NKG2D NKE bispecific antibody with a modified Fc domain to enhance FcγR binding. The molecule’s design is intended to engage NK cells through the simultaneous binding to B7-H3 on tumor cells and the activating receptors NKG2D and CD16. Additionally, NKEs may provide co-stimulation to T cells through NKG2D expressed on T cells.

In vitro, B7-H3 x NKG2D NKEs activated NK cells, enhanced NK cell mediated lysis of tumor cells and provided co-stimulation to T cells. Additionally, in vitro anti-tumor activity was enhanced when combined with proinflammatory cytokines: an analog of the IL15-Fc cytokine XmAb306 and the IL12-Fc cytokine XmAb662.

On November 12, 2021 Moleculin Biotech, Inc., (Nasdaq: MBRX) (Moleculin or the Company), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors and viruses, reported that Walter V. Kemp, Founder, President, CEO and Chairman and Dr. John Paul Waymack, Senior Chief Medical Officer will participate in the Virtual Investor Roundtable Event on Thursday, November 18, 2021 at 11:00 AM ET (Press release, Moleculin, NOV 12, 2021, View Source [SID1234595485]).

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Joining the Company’s management team for the roundtable discussion will be Sant P. Chawla, MD, Director, Sarcoma Oncology Center, Director, Cancer Center of Southern California.

As part of the virtual event, the Company will provide a brief presentation, followed by a moderated Roundtable discussion and an interactive Q&A session. In addition to the moderated portion of the event, all investors and interested parties will have the opportunity to submit questions live during the event. Interested parties may also pre-submit questions in advance of the live event, which can be sent via the conference website at virtualinvestorco.com. The Company will answer as many questions as possible during the event.

A live video webcast of the Roundtable Event will be available on the Events page of the Investors section of the Company’s website (moleculin.com). A webcast replay will be available two hours following the live presentation and will be accessible for one year.