On January 31, 2022 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a clinical-stage cancer immunotherapy company developing novel biotherapeutics targeting immunosuppressive myeloid checkpoints, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for IO-202, a first-in-class antibody targeting leukocyte immunoglobulin-like receptor B4 (LILRB4, also known as ILT3), for the treatment of solid tumors (Press release, Immune-Onc Therapeutics, JAN 31, 2022, View Source [SID1234607529]).

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Myeloid cells are abundant and often immune suppressive in the solid tumor microenvironment. The LILRB4 receptor is expressed on monocytic myeloid cells, including dendritic cells, and contributes to a tolerogenic myeloid cell phenotype, resulting in decreased tumor immune surveillance. In preclinical data presented at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, IO-202 was found to enhance dendritic cell function and T cell activation in vitro and promote anti-tumor immunity in a solid tumor model in vivo. These data provided a strong rationale to evaluate the therapeutic potential of IO-202 as a myeloid checkpoint inhibitor in solid tumors.

"The FDA clearance to begin our Phase 1 study for IO-202 in solid tumors is a major milestone for Immune-Onc, which represents the third IND for our pipeline and the second for IO-202," said Charlene Liao, Ph.D., chief executive officer of Immune-Onc. "We know that high LILRB4 expression on myeloid cells infiltrating solid tumors contributes to tumor immune evasion. IO-202 is a first-in-class myeloid checkpoint inhibitor targeting LILRB4, which may provide therapeutic benefit to multiple solid tumor types where evasion of the immune system allows disease to progress and create resistance to therapy, including to T cell checkpoint inhibitors. We look forward to advancing IO-202 into the clinic to evaluate its potential as a monotherapy and in combination with an anti-PD-1 in patients with solid tumors."

The Phase 1, multicenter, dose-escalation and dose expansion study will consist of a monotherapy cohort and a combination therapy cohort to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of IO-202 alone and in combination with pembrolizumab, an anti-PD-1 antibody, followed by indication-specific expansion cohorts to be treated with IO-202 in combination with pembrolizumab at the recommended Phase 2 dose. Various biomarkers will be assessed to enable a mechanistic understanding of clinical data and inform future trials. This study may also provide an opportunity to identify preliminary efficacy signals.

ABOUT LILRB4 (also known as ILT3)

LILRB4, also known as ILT3, is an immune inhibitory transmembrane protein found on monocytic myeloid cells, including dendritic cells. LILRB4 inhibits antigen-presenting cell activation, resulting in immune tolerance. LILRB4 is also expressed on certain hematologic cancer cells and monocytic myeloid cells in the solid tumor microenvironment. Immune-Onc and The University of Texas published pioneering research in Nature illuminating the role of LILRB4 in immune suppression and tumor infiltration in acute myeloid leukemia (AML) and presented the rationale for targeting LILRB4 in solid tumors at the AACR (Free AACR Whitepaper) Annual Meeting 2021.

ABOUT IO-202

IO-202 is a first-in-class LILRB4 antagonist antibody with broad potential as an immunotherapy in both blood cancers and solid tumors. In hematologic malignancies, preclinical studies showed that IO-202 converts a "don’t kill me" to a "kill me" signal by activating T cell killing and converts a "don’t find me" to a "find me" signal by inhibiting infiltration of blood cancer cells. In solid tumors, preclinical data showed that IO-202 enhances dendritic cell function and T cell activation in vitro and inhibits tumor growth in a solid tumor model in vivo.

IO-202 is currently in Phase 1 clinical development for the treatment of AML and chronic myelomonocytic leukemia (CMML). The U.S. Food and Drug Administration granted IO-202 Orphan Drug Designations for treatment of AML in 2020. The company has received IND clearance to evaluate IO-202 in solid tumors in January 2022.

On January 31, 2022 Sierra Oncology, Inc. (Nasdaq: SRRA), a late-stage biopharmaceutical company dedicated to delivering targeted therapies for rare cancers, reported the closing of its previously announced underwritten public offering of 4,074,075 shares of its common stock at a price to the public of $27.00 per share and, in lieu of shares of common stock, to a certain investor, pre-funded warrants to purchase up to 925,925 shares of common stock at a price to the public of $26.999 per pre-funded warrant, which represents the per share public offering price for the common stock less the $0.001 per share exercise price for each pre-funded warrant (Press release, Sierra Oncology, JAN 31, 2022, View Source [SID1234607528]). The gross proceeds to Sierra Oncology from the offering were approximately $135.0 million, before deducting underwriting discounts and commissions and other offering expenses. Net proceeds to Sierra Oncology from the offering were approximately $126.6 million after deducting underwriting discounts and commissions and other offering expenses. Sierra Oncology intends to use the net proceeds of the offering to prepare for potential commercialization of momelotinib, clinical development of its other product candidates, research, clinical and process development and manufacturing of its product candidates, working capital, and capital expenditures and other general corporate purposes.

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Jefferies and Cantor are acting as the joint book-running managers and representatives of the underwriters for the offering. LifeSci Capital, Oppenheimer & Co. and H.C. Wainwright & Co. are acting as lead managers for the offering.

A shelf registration statement on Form S-3 relating to the securities offered in the public offering described above was filed with the Securities and Exchange Commission (SEC) on November 5, 2021 and declared effective by the SEC on November 12, 2021. A final prospectus supplement and accompanying prospectus relating to the offering have been filed with the SEC and are available on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and accompanying prospectus may also be obtained by contacting Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by telephone at (877) 821-7388, or by email at [email protected]; or Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Avenue, New York, New York 10022, or by e-mail at [email protected].

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

On January 31, 2022 The Janssen Pharmaceutical Companies of Johnson & Johnson reported the submission of a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) seeking approval of teclistamab for the treatment of patients with relapsed or refractory multiple myeloma (RRMM) (Press release, Johnson & Johnson, JAN 31, 2022, View Source [SID1234607527]). Teclistamab is an investigational, off-the-shelf, T-cell redirecting, bispecific antibody targeting both B-cell maturation antigen (BCMA) and CD3.1

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"Despite the significant progress that has been made in the treatment of multiple myeloma, it remains an incurable cancer, with approximately half of newly diagnosed patients not reaching five-year survival and almost a third dying within one year of diagnosis," said Edmond Chan MBChB M.D. (Res), Senior Director, EMEA Therapeutic Area Lead Haematology, Janssen-Cilag Limited. "Today’s submission is an important step forward in our mission to improve outcomes for people living with multiple myeloma, where the need for new treatment strategies remains high."

In December 2021, the EMA granted accelerated assessment for teclistamab. Accelerated assessment reduces the timeframe for the Committee for Medicinal Products for Human Use (CHMP) to review a MAA and is granted when a medicinal product is of major interest for public health and therapeutic innovation.2

The submission to the EMA is supported by data from MajesTEC-1 (NCT03145181, NCT04557098), an open-label, multicentre clinical trial evaluating the safety and efficacy of teclistamab in adults with RRMM.1 Efficacy outcomes assessed included overall response rate, very good partial response and complete response, using the International Myeloma Working Group (IMWG) criteria.3 Safety outcomes evaluated included dose limiting toxicity and the number of participants with adverse events as a measure of safety and tolerability.4 Updated MajesTEC-1 data were recently presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2021 annual meeting.1

"We are pleased to announce the submission of teclistamab to the European Medicines Agency. Once again, this shows our commitment to continue to provide innovative, transformative therapies for patients with relapsed or refractory multiple myeloma," said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC.

The application to the EMA follows a Biologics License Application (BLA) submitted to the U.S. Food and Drug Administration (FDA) seeking approval of teclistamab for the treatment of RRMM. Additionally, a MAA for teclistamab was recently submitted to the Swiss Agency for Therapeutic Products (Swissmedic) through a Type A Project Orbis submission. Project Orbis is an initiative of the FDA Oncology Center of Excellence, and provides a framework for concurrent submission and review of oncology products among international partners, with the aim of facilitating faster patient access to high-impact, innovative cancer therapies across multiple countries.5 A Type A application is submitted concurrently (within 30 days) to the FDA and the Project Orbis Partners (POPs), allowing for maximal collaboration during the review phase and the possibility of concurrent approval decisions.5

About Teclistamab
Teclistamab is an investigational, off-the-shelf, T-cell redirecting bispecific antibody targeting both BCMA and CD3. BCMA is expressed at high levels on multiple myeloma cells.6,7,8,9,10 Teclistamab redirects CD3-positive T-cells to BCMA-expressing myeloma cells to induce killing of tumour cells.11

Teclistamab is currently being evaluated in several monotherapy and combination studies.3,12,13,14,15 In 2020, the European Commission (EC) and the U.S. FDA each granted teclistamab Orphan Drug Designation for the treatment of multiple myeloma. In January 2021 and June 2021, teclistamab received a PRIority MEdicines (PRIME) designation by the EMA and Breakthrough Therapy Designation (BTD) by the FDA, respectively. PRIME offers enhanced interaction and early dialogue to optimise drug development plans and speed up evaluation of cutting-edge, scientific advances that target a high unmet medical need.16 The FDA grants BTD to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition and is based on preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.17

About Multiple Myeloma
Multiple myeloma is currently an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.18,19 When damaged, these plasma cells change and grow out of control. Abnormal plasma cells can crowd out or suppress the growth of other healthy cells in the bone marrow.19 In Europe, more than 50,900 people were diagnosed with multiple myeloma in 2020, and more than 32,500 patients died.20 While some patients with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, or kidney failure.21

On January 31, 2022 Leica Biosystems, a cancer diagnostics company, reported that it has entered into an agreement with Leap Therapeutics (NASDAQ: LPTX), a biotechnology company, to develop a companion diagnostic to detect Dickkopf-related protein 1 (DKK1) (Press release, Leica Biosystems, JAN 31, 2022, View Source [SID1234607526]). The assay will be used to support clinical development of Leap Therapeutics’ anti-DKK1 cancer therapy, DKN-01, currently being studied in clinical trials.

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DKK1 is a protein often implicated in cancer, enabling tumor cells to suppress the immune system and lead to unregulated growth. Overexpression of DKK1 is associated with poor survival in cancer patients.

Leap Therapeutics is currently advancing the development of DKN-01, a humanized monoclonal antibody that targets DKK1, to treat cancer. The company is currently studying the drug as part of a combination therapy regimen in a Phase 2 clinical trial in patients with gastric or gastroesophageal junction cancer.

The assay developed by Leica Biosystems will utilize RNAscope technology from Bio-Techne on the BOND-III Automated Staining System, which allows for detection of DKK1 with high sensitivity and specificity, to help identify patients most likely to benefit from DKN-01 treatment.

"Companion Diagnostics are a step toward treating cancer patients based on the biomarker makeup of their disease," said Rachel Skelton, Senior Director of Pharma Partnerships at Leica Biosystems. "We are excited to partner with Leap to advance cancer care."

Companion Diagnostics are tests that may be used to determine if a patient’s tumor has the biomarker that will predict the outcome of a treatment with a specific therapy. With expertise in assay development, regulatory approval and commercialization, the Leica Biosystems Companion Diagnostics team partners with pharmaceutical companies to develop assays for a diverse range of technologies. Our flexible approach to partnerships, along with the robust capabilities of the BOND Advance Staining Solutions, supports our mission of Advancing Cancer Diagnostics, Improving Lives.

"DKK1 is novel and broadly applicable biomarker that is often elevated in patients with poor outcomes," said Jason Baum, Vice President and Head of Translational Medicine at Leap Therapeutics. "Patients whose tumors express elevated levels of DKK1 have shown compelling clinical responses when treated with DKN-01-based regimens. We are pleased to partner with Leica to advance the clinical development of our therapy and improve patient lives."

On January 31, 2022 Imugene Limited (ASX:IMU) a clinical stage immuno-oncology company reported it has received a Notice of Grant from the Japanese Patent Office for Patent Application number 2019-507161 which protects its oncolytic virotherapy CF33, including VAXINIA (CF33-hNIS) and CHECKVacc (CF33-hNIS-antiPDL1) (Press release, Imugene, JAN 31, 2022, View Source [SID1234607525]).

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The patent titled "CHIMERIC POXVIRUS COMPOSITION AND USES THEREOF" (inventors Yuman Fong and Nanhai Chen from the City of Hope) protects the method of composition and method of use of Imugene’s licensed oncolytic virotherapy to 2037.

CF33 is a chimeric vaccinia poxvirus from the lab of inventor Professor Yuman Fong, Chair of Sangiacomo Family Chair in Surgical Oncology at City of Hope, and a noted expert in the oncolytic virus field.

Oncolytic viruses (OVs) are designed to both selectively kill tumour cells and activate the immune system against cancer cells, with the potential to improve clinical response and survival. Imugene MD & CEO Leslie Chong said:

"Imugene receiving this patent grant for the CF33 family of oncolytic viruses from the Japanese patent office is a crucial step forward and is the first of many expected patent grants from multiple countries. The start of our VAXINIA and CHECKVacc OV studies are a significant milestone for clinicians treating patients faced with the challenge of solid tumour cancers."