On March 9, 2022 Oncorus, Inc. (Nasdaq: ONCR), a viral immunotherapies company focused on driving innovation to transform outcomes for cancer patients, reported fourth quarter and full year 2021 financial results and highlighted recent achievements and developments (Press release, Oncorus, MAR 9, 2022, View Source [SID1234609748]).

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"In 2021, Oncorus made meaningful progress advancing our pipeline of next-generation, systemically active viral immunotherapies. With a broad range of activities across both our innovative HSV and selectively self-amplifying vRNA/LNP platforms, we are well-positioned to execute on multiple clinical and preclinical catalysts this year as we build out our differentiated portfolio of intratumorally and intravenously administered viral immunotherapies," said Theodore (Ted) Ashburn, M.D., Ph.D., President and Chief Executive Officer of Oncorus. "We remain on track to report multiple clinical-stage milestones this year, with both additional ONCR-177 data from the surface lesion monotherapy expansion and the initial combination expansion data with KEYTRUDA expected in the second half of 2022. We also continue to progress our earlier stage programs, with ONCR-021 advancing into IND-enabling studies, while we simultaneously build out our Andover manufacturing facility to enable expansion of our portfolio."

Fourth Quarter 2021 and Recent Business Highlights

Presented initial data from ongoing Phase 1 clinical trial of ONCR-177 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting. In November 2021, Oncorus presented initial safety, tolerability, immune activation and clinical response data from its ongoing Phase 1 open-label, multi-center, dose escalation and expansion clinical trial of ONCR-177, an intratumorally (iTu) administered Herpes Simplex Virus (HSV) viral immunotherapy, being developed for multiple solid tumor indications. 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 the Recommended Phase 2 Dose (RP2D) across multiple indications (cutaneous melanoma, squamous cell carcinoma of the head and neck and mucosal melanoma) experienced clinical benefit after two doses of ONCR-177. The Phase 1 presentation at SITC (Free SITC Whitepaper) marked Oncorus’ first reporting of human data from its HSV platform.

On track to report additional ONCR-177 monotherapy and combination data in 2022. The Phase 1 open-label, multi-center, dose escalation and expansion clinical trial is designed to evaluate the safety and tolerability of ONCR-177 alone and in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in patients with advanced and/or refractory cutaneous, subcutaneous or metastatic nodal solid tumors or with liver metastases of solid tumors. The Company has completed enrollment in the dose expansion portion of the trial and continues to enroll patients in the combination cohort. Future data readouts are expected in the second half of 2022 and will include both additional surface lesion monotherapy expansion data for ONCR-177 and initial surface lesion combination expansion data for ONCR-177 administered with KEYTRUDA.

Signed exclusive licensing agreement with Gaeta Therapeutics for use of locally delivered Interleukin-12 (IL-12) via oncolytic viral expression in combination with immune checkpoint inhibitors. In November 2021, Oncorus signed an exclusive licensing agreement with Gaeta Therapeutics for the use of locally delivered IL-12 via oncolytic viral expression in combination with immune checkpoint inhibitors, including CTLA-4, PD-1 or PD-L1 checkpoint blockade.

Presented preclinical data on ONCR-GBM at the International Oncolytic Virus Conference (IOVC) 2021. In November 2021, Oncorus presented a preclinical poster describing the design and evaluation of multiple features that will be incorporated into the ONCR-GBM program, including robust anti-tumor activity observed with IL-12 and a proprietary PD-1 antagonist nanobody. Leveraging its HSV platform, Oncorus is pursuing ONCR-GBM to specifically target brain cancer, including glioblastoma multiforme (GBM). The company is utilizing its knowledge of microRNA expression to engineer a microRNA attenuation strategy to protect healthy brain tissue and to select a rational combination of payloads intended to address both the cancer itself and the specific drivers of immune suppression in the brain.

Selectively self-amplifying viral RNA (vRNA) immunotherapy platform and clinical candidates, ONCR-021 and ONCR-788, continue to progress. Oncorus continues to progress its selectively self-amplifying vRNA/lipid nanoparticle (LNP) platform and two clinical candidates, ONCR-021 and ONCR-788, which employ the company’s pioneering IV-administered approach of encapsulating the genomes of RNA viruses known to kill cancer cells (i.e., oncolytic viruses, or OVs) in LNPs. Oncorus is currently initiating GLP safety and tolerability studies for ONCR-021 and anticipates submitting an investigational new drug application (IND) for this program in mid-2023. The company is also conducting preliminary non-GLP safety and tolerability studies for ONCR-788. Oncorus plans to investigate its novel selectively self-amplifying vRNA immunotherapies in multiple therapeutic areas, including cancers of the lung, both as monotherapy and in combination with immune checkpoint inhibitors and possibly other cancer treatments.

Strengthened executive leadership team with promotion of John Goldberg, M.D., to Chief Medical Officer. In February 2022, Oncorus announced the promotion of John Goldberg, M.D. to Chief Medical Officer. Dr. Goldberg responsibilities will continue to include oversight of all clinical studies, drug development and regulatory strategies. Dr. Goldberg previously served as Oncorus’ Senior Vice President of Clinical Development since 2018.
Fourth Quarter 2021 Financial Results

Cash and cash equivalents and investments totaled $123.9 million as of December 31, 2021 compared to $130.3 million as of December 31, 2020.

Research and development expenses for the quarter ended December 31, 2021 were $14.3 million compared to $7.6 million for the corresponding quarter in 2020. The increase was primarily attributable to employee compensation costs, which was driven by increased headcount and increased stock-based compensation, increased rent expense related to the company’s manufacturing facility and increased development costs related to the company’s nominated candidates.

General and administrative expenses for the quarter ended December 31, 2021 were $5.6 million compared to $4.0 million for the corresponding quarter in 2020. The increase was primarily attributable to employee compensation costs, including higher stock-based compensation, increased headcount and increased salary and related expenses. General and administrative expenses also increased due to higher insurance expense and professional and consultant expenses related to operating as a public company.

Net loss attributable to common stockholders for the quarter ended December 31, 2021 was $19.8 million, or $0.77 per share, as compared to a net loss attributable to common stockholders of $11.8 million, or $0.56 per share for the corresponding quarter in 2020. The increase in the net loss was due to increased expenses associated with the company’s growth and the increase in net loss per share was a result of the increased net loss offset by additional shares issued by the Company in a public stock offering in February 2021.
Financial Guidance

Based upon its current operating plans and cash and cash equivalents and investments, Oncorus expects to have sufficient capital to fund its operating expenses and capital expenditure requirements into late 2023.

On March 9, 2022 SHINE Technologies, LLC (SHINE), a next-generation nuclear technology company, and ImaginAb Inc. (ImaginAb), a market-leading global biotechnology company focused on developing next generation immuno-oncology imaging agents and therapeutic radiopharmaceuticals (RPT), reported the signing of a clinical supply agreement (Press release, Shine Medical Technologies, MAR 9, 2022, View Source [SID1234609771]). Under the terms of this agreement, SHINE will provide ImaginAb with highly pure, non-carrier-added (n.c.a.) lutetium-177 (Lu-177) to support the company’s preclinical and clinical needs in the development of RPTs targeting various cancers.

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"We are thrilled to continue to partner with leading biotechnology companies like ImaginAb in the mission to drive innovation of cancer therapeutics," said Greg Piefer, SHINE’s founder and CEO. "We are proud to deliver Lu-177 and other medical isotopes as they play a major role for biotechnology companies like ImaginAb to continue to innovate treatment solutions for critically ill patients."

SHINE’s Therapeutics division produces n.c.a. Lu-177, a low-energy beta-particle emitter, which can be paired with a targeting molecule (such as an antibody or peptide) to directly target and irradiate cancer cells. SHINE’s fusion technology and proprietary medical isotope production is expected to scale without supply chain limitations experienced recently due to nuclear reactor shutdowns. The result: better meeting the needs of n.c.a. Lu-177 based therapies as they commercialize.

ImaginAb is developing radiopharmaceutical therapy agents based on proprietary minibody and cys-diabody platform technologies. This platform possesses the highly tumor target selective features of larger antibodies while offering highly tunable pharmacokinetics providing rapid clearance from non-target tissues.

Ian Wilson, CEO of ImaginAb, commented: "Having a robust supply chain is key to the implementation of radiopharmaceutical therapy, and partnering with SHINE for our Lu-177 supply offers access to what we feel will become one of the largest and most reliable sources in the world for this isotope. Lu-177 is a great fit for our platform technologies. We are very excited about our upcoming clinical programs in oncology radiopharmaceutical therapies."

SHINE will begin supplying ImaginAb with n.c.a. Lu-177 immediately for the company’s development activities and for therapeutic clinical trials planned for 2023. More information on clinical trial results will be provided directly by ImaginAb.

On March 9, 2022 AIM ImmunoTech Inc. (NYSE: American AIM) ("AIM" or the "Company"), an immuno-pharma company focused on the research and development of therapeutics to treat multiple types of cancers, immune disorders, and viral diseases, including COVID-19, the disease caused by the SARS-CoV-2 virus, reported that oncology experts from Roswell Park Comprehensive Cancer Center will present findings from two ongoing clinical studies involving an AIM ImmunoTech Inc (Press release, AIM ImmunoTech, MAR 9, 2022, View Source [SID1234609787]). drug candidate, Ampligen (also known as rintatolimod) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, being held April 8-13, 2022, in New Orleans, Louisiana.

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Research led by Roswell Park medical oncologists Shipra Gandhi, MD, and Sarbajit Mukherjee, MD, MS, in collaboration with senior investigator Pawel Kalinski, MD, PhD, Chair of Immunology at Roswell Park, has been accepted for presentation as late-breaking poster abstracts at the meeting.

Details of the abstract and late-breaking poster presentations are as follows:

Title: Initial results of a phase II study evaluating a chemokine-modulatory (CKM) regimen in patients with colorectal cancer metastatic to the liver
Presenter: Sarbajit Mukherjee, MD, MS
Abstract Number: 22-LB-7312
Session: Phase II Clinical Trials 1, presentation CT105
Presentation Type: Late-breaking poster presentation
Session Date and Time: Monday, April 11, 2022, from 9 a.m. 12:30 p.m. CDT
Location: Poster 2, Section 33

Title: Systemic Rintatolimod and Interferon-α2b selectively reprogram local tumor microenvironment in patients with metastatic triple negative breast cancer for enhanced influx of cytotoxic T-lymphocytes but not regulatory T-cells
Presenter: Shipra Gandhi, MD
Abstract Number: 22-LB-7620
Session: Phase I Clinical Trials 1, presentation CT145
Presentation Type: Late-breaking poster presentation
Session Date and Time: Monday, April 11, 2022, from 1:30 to 5 p.m. CDT
Location: Poster 12, Section 35

The late-breaking and clinical trials abstract titles and authors are now available on the AACR (Free AACR Whitepaper) Online itinerary planner. The late-breaking and clinical trials abstract text is under embargo until April 8, 2022 at 1:00 p.m. ET.

On March 9, 2022 NorthStar Medical Radioisotopes, LLC, a global innovator in the development, production and commercialization of radiopharmaceuticals used for therapeutic applications and medical imaging, and Convergent Therapeutics, Inc., a clinical stage radiopharmaceutical company, reported the signing of a long-term supply agreement for the therapeutic medical radioisotope, actinium-225 (Ac-225) (Press release, NorthStar Medical Radiostopes, MAR 9, 2022, View Source [SID1234609818]). Under terms of the agreement, NorthStar will provide Convergent with its environmentally preferred, high purity non-carrier-added (n.c.a.) Ac-225. Convergent will use NorthStar’s Ac-225 to radiolabel its lead asset, CONV01-α, a prostate-specific membrane antigen (PSMA)-targeted monoclonal antibody, currently being investigated as a potential ground-breaking treatment for prostate cancer.

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Ac-225 is a high energy alpha-emitting radioisotope of increasing interest for clinical studies investigating the use of targeted radiopharmaceutical therapy (RPT), which combines select molecules with therapeutic radioisotopes, such as Ac-225, to directly target and deliver therapeutic doses of radiation to destroy cancer cells in patients with serious disease. Ac-225 carries sufficient radiation to cause cell death in a localized area of targeted cells, while its half-life limits unwanted radioactivity in patients. Clinical research and commercial use of Ac-225 are severely constrained by chronic short supply due to limitations of current production technology. NorthStar is positioned to be the first commercial-scale producer of Ac-225 for advancing clinical research and commercial radiopharmaceutical products. The Company will use its environmentally-sound electron accelerator technology to produce n.c.a. Ac-225 that is free of long-lived radioactive contaminants and byproducts associated with other production methods, which pose regulatory and waste management challenges for hospitals and health systems.

"NorthStar is applying the same development expertise to rapidly advance large-scale production of n.c.a. Ac-225 that has positioned us at the forefront of U.S. radioisotope production as the only commercialized producer of the important medical radioisotope molybdenum-99 (Mo-99)," said Stephen Merrick, President and Chief Executive Officer of NorthStar Medical Radioisotopes. "Like all NorthStar processes, our n.c.a. Ac-225 production technology is environmentally sustainable and non-uranium based, utilizing state-of-the-art electron beam accelerator production that provides increased capacity and scheduling flexibility. Facility design is complete and we expect construction to be underway soon on our dedicated Actinium-225 Production facility, with initial production of radiochemical grade Ac-225 planned for late 2023, and a Drug Master File to be submitted to the FDA in 2024, which, upon acceptance by the FDA, will allow NorthStar to provide cGMP grade Ac-225. We are very pleased to enter this Ac-225 supply agreement with Convergent Therapeutics, and we look forward to working with them moving forward. Our companies share a vision of developing and delivering innovative technology to drive research and ensure clinical availability of targeted radiopharmaceutical therapies for patients with cancer."

"Convergent has demonstrated that dual targeting of surface cancer molecules, like prostate-specific membrane antigen (PSMA), improves antitumor efficacy and may represent a truly disruptive and advantageous therapeutic option to treat prostate cancer," said Philip Kantoff, M.D., Chief Executive Officer of Convergent Therapeutics. "Our lead candidate, CONV01-α, is a monoclonal antibody radiolabeled with Ac-225, and is specifically designed to bind to PSMA, which is highly expressed in most prostate cancer. Once bound, CONV01-α becomes internalized, enabling delivery of supra-additive therapeutic doses of radiation directly into prostate cancer cells. The power of labeling CONV01-α with an alpha-emitting radioisotope such as Ac-225 is in its ability to maximize antitumor impact while minimizing radiation to adjacent tissue. NorthStar is our ideal partner for Ac-225 supply based on their leadership experience and commercial expertise in cutting-edge, accelerator-based radioisotope production technology. We look forward to working with NorthStar to supply Ac-225 for our clinical studies and future commercialization needs as we seek to deliver highly transformative treatments for patients with prostate and other cancers."

On March 9, 2022 I-Mab (the "Company") (Nasdaq: IMAB), a clinical-stage biopharmaceutical company committed to the discovery, development, and commercialization of novel biologics, reported that two poster presentations featuring translational research data of enoblituzumab (also known as TJ271) and preclinical data of TJ-C64B will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting, to be held April 8-13, 2022 (Press release, I-Mab Biopharma, MAR 9, 2022, View Source [SID1234609832]).

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"We continue to make significant progress in advancing our innovative pipeline to generate the next wave of novel cancer therapeutics for patients around the world," said Dr. Andrew Zhu, President of I-Mab. "The translational research data of enoblituzumab provide compelling rationale to further investigate combination therapy for increased clinical efficacy against multiple cancer types. In addition, the preclinical data of TJ-C64B provide the underlying mechanism of action for further clinical development of this novel bispecific antibody."

Enoblituzumab is a highly differentiated humanized monoclonal antibody directed against the immune regulator B7-H3, which has been associated with poor prognosis and is widely expressed in multiple cancers. Enoblituzumab mediates the antibody-dependent killing of cancer cells and has demonstrated strong anti-tumor activity in preclinical studies. Currently, I-Mab is conducting a phase 2 trial in China for enoblituzumab in combination with pembrolizumab (Keytruda) in patients with solid tumors, including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), and other selected cancers.

TJ-C64B is the third bispecific antibody with a conditional T cell engager based on 4-1BB-activation platform. It binds simultaneously to Claudin 6 (CLDN6)-expressing cancer cells and the costimulatory molecule 4-1BB. CLDN6 is a tight junction transmembrane protein hardly detected in adult normal tissues, but aberrantly expressed in a variety of tumors, including ovarian cancer, testicular cancer, hepatocellular and lung adenocarcinoma. TJ-C64B is designed to conditionally activate T cells through 4-1BB stimulation upon CLDN6 engagement, positioning it as a potential novel immunotherapy for ovarian cancer and other CLDN6 positive tumors.

Details for the 2022 AACR (Free AACR Whitepaper) presentations are as follows:

Abstract Title:

Inhibition of B7-H3 by Enoblituzumab Elicits Anti-Tumor Immune Modulation in Both Innate and Adaptive Immunity

Abstract #:

4228

Presenting author:

Xuejun Liu, PhD

Date and Time:

Wednesday, Apr 13, 2022

9:00 AM – 12:30PM (EST)

Summary:

The function of B7-H3 and enoblituzumab in regulating immune response was investigated in human PBMCs using the Nanostring nCounter platform for gene expression and CyTOF mass cytometry for immunophenotyping.
Data confirmed the immunosuppressive function of B7-H3 and demonstrated the immunoregulatory function of enoblituzumab as evidenced by the activation of cytolytic T cell and NK cells, reinvigoration of exhausted cells, and suppression of M2-like myeloid cells.
Enoblituzumab exhibited tumor killing activity against ES-2, a B7-H3-expressing ovarian cancer cell line in vitro. Consistent with the enoblituzumab-associated increased 4-1BB expression in T and NK cells, activation of 4-1BB by urelumab, a 4-1BB agonist, further enhanced enoblituzumab-mediated tumor killing activity.
These findings provide rationale for combination therapy with blockade of B7-H3 by enoblituzumab with other immunotherapies to achieve increased clinical efficacy against multiple cancer types.
Abstract Title:

Discovery of a Novel Claudin 6 x 4-1BB Bispecific Antibody with Potent Anti-Tumor Activity through Conditional 4-1BB Activation

Abstract #:

5558

Presenting author:

Jian Li, PhD

Date and Time:

Friday, Apr 8, 2022

1:00 PM (EST)

Summary:

Data have confirmed the novel CLDN6-targeted 4-1BB bispecific antibody TJ-C64B to induce potent 4-1BB stimulation and anti-tumor activity in a CLDN6-dependent manner while minimizing the risk of liver toxicity.
In humanized 4-1BB syngeneic mouse model, TJ-C64B exhibited significant tumor growth inhibition, associated with elevation in tumor infiltrating CD45 and CD8 cells as well as CD8/Treg ratio.
From the safety perspective, there were no significant changes in liver enzymes following repeated TJ-C64B administration, suggesting a minimal risk for liver toxicity commonly induced by other 4-1BB agonist antibodies.
Taken together, these data support further development of TJ-C64B towards clinical development subsequently.
About Enoblituzumab

Enoblituzumab is an investigational Fc-optimized monoclonal antibody that targets B7-H3, a member of the B7 family of immune regulator proteins. B7-H3 is widely expressed by many different tumor types and may play a key role in regulating the immune response to various types of cancer. Enoblituzumab has been or is currently being evaluated in clinical trials as a monotherapy or in combination with anti-PD-1-based therapies in patients with B7-H3-expressing cancers. I-Mab licensed the development and commercial rights from MacroGenics for Greater China.

About TJ-C64B

TJ-C64B is a bispecific antibody simultaneously targeting tumor associated antigen Claudin 6 (CLDN6) and costimulatory molecule 4-1BB for CLDN6+ tumor treatment. TJ-C64B is specifically designed to conditionally activate T cells through 4-1BB stimulation upon CLDN6 engagement, providing a more localized activation of the immune system with good efficacy and reduced systemic toxicity. TJ-C64B is currently under preclinical development.