On April 5, 2022 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of therapeutics designed to activate immune response to cancers and infections, reported receipt of a $5M clinical milestone payment for AGEN2373 (conditionally active CD137 agonist) (Press release, Agenus, APR 5, 2022, View Source [SID1234611464]). AGEN2373 is being evaluated in a Phase 1b combination study with botensilimab (Fc-enhanced anti-CTLA-4), in melanoma patients who had relapsed on, or were refractory to, prior anti-PD-1 therapy.

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"The majority of patients treated with anti-PD-1 progress within a year and are in need of more effective treatment options," said Steven O’Day, MD, Chief Medical Officer of Agenus. "Botensilimab has shown promising activity in a wide range of treatment-resistant cancers, including melanoma. The rationale to combine botensilimab and AGEN2373 is based on preclinical evidence we reported of enhanced tumor control with this approach in a PD-1 resistant melanoma model. This study represents a rationally designed combination strategy to bring novel therapies to cancer patients."

AGEN2373 has demonstrated preliminary clinical benefit and has been well tolerated without signs of liver toxicity, an adverse event that has impacted competitor antibodies in the clinic. Gilead currently has an exclusive option to license AGEN2373. Agenus retains the right to opt-in to share Gilead’s development and commercialization costs in the United States in exchange for a 50:50 profit share and US co-commercialization rights.

References

A. Tolcher et al., Initial findings of the first-in-human Phase I study of AGEN2373, a conditionally active CD137 agonist antibody, in patients (pts) with advanced solid tumors. Presented at the ASCO (Free ASCO Whitepaper) 2021 Virtual Meeting.

C. Galand et al., AGEN2373 is a CD137 agonist antibody designed to leverage optimal CD137 and FcγR co-targeting to promote antitumor immunologic effects. Presented at the SITC (Free SITC Whitepaper) 2020 Virtual Meeting.

About AGEN2373
AGEN2373 is a fully human monoclonal antibody designed to boost the immune response to cancer cells by enhancing CD137 co-stimulatory signaling in activated immune cells. The unique binding properties of AGEN2373 are expected to limit its activity outside of the tumor site and mitigate toxicities that may be associated with systemic activation of CD137 in humans.

About Botensilimab
Botensilimab (also known as AGEN1181) is a next-generation, Fc-enhanced, immunoglobulin G1 (IgG1) antibody designed to block CTLA-4 (cytotoxic T-lymphocyte associated antigen 4) inhibitory function from interacting with its ligands CD80 and CD86. The Fc region of the antibody was engineered to enhance immune activation and tumor killing, improve safety, and benefit a broader patient population versus first-generation anti CTLA-4 antibodies. CTLA-4 is a negative regulator of immune activation that is considered a foundational target within the immuno-oncology market.

On April 5, 2022 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported that it will present three posters highlighting data for XMT-1660, XMT-2056, and the Immunosynthen ADC platform at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 to be held in New Orleans, Louisiana from April 8-13, 2022 (Press release, Mersana Therapeutics, APR 5, 2022, View Source [SID1234611463]).

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"ADC innovation is at the core of Mersana’s strategy, and we have made significant progress in building out an innovative pipeline of potential cancer medicines. Our preclinical data show the potential of XMT-1660 in a range of B7-H4 expressing tumors and the power of our Dolasynthen platform," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. "The preclinical profile of XMT-2056 as monotherapy and in combination with standard of care therapies in both HER2-high and HER2-low expressing models reinforces the differentiation of the Immunosynthen platform. We look forward to advancing both molecules into the clinic in mid-2022."

XMT-1660 is a Dolasynthen ADC targeting B7-H4, a target selectively expressed on tumors in areas of high unmet medical need, including breast, endometrial, ovarian and other cancers. The data show that a single dose of XMT-1660 has anti-tumor activity in both triple-negative breast cancer (TNBC) and estrogen receptor (ER)-positive breast cancer xenograph models. Higher B7-H4 expression is associated with greater anti-tumor activity of XMT-1660 in preclinical studies. Mersana expects a Phase 1 clinical trial for XMT-1660 to start in mid-2022.

XMT-2056, Mersana’s first Immunosynthen STING-agonist ADC, targets a novel epitope of HER2, and is designed to offer a differentiated and complementary therapeutic approach to the treatment of HER2-expressing tumors. The preclinical data presented show that XMT-2056 demonstrates robust anti-tumor activity as a monotherapy in both HER2-high and HER2-low expressing models. XMT-2056’s complementary mechanism of action results in increased efficacy in combination with trastuzumab, pertuzumab, anti-PD-1, or trastuzumab deruxtecan in preclinical studies. Mersana expects to initiate a Phase 1 clinical trial of XMT-2056 in mid-2022.

Immunosynthen is Mersana’s immunostimulatory ADC platform designed to take ADCs beyond traditional cytotoxic drugs to targeted stimulation of the innate immune system. Data show that anti-tumor activity of Immunosynthen STING-agonist ADCs involves the targeted activation of the STING pathway in an antigen binding-dependent manner in both tumor-resident immune cells and in tumor cells. In addition to delivery to the tumor cell via antigen binding and internalization, data from multiple models demonstrate Fcγ-R1 is the major receptor that mediates delivery to a specific population of myeloid cells resident in primary human tumors, eliciting potent anti-tumor responses in preclinical studies.

Details of the presentations are as follows:

Poster Title: Anti-tumor effect of XMT-1660, a B7-H4 targeting antibody drug conjugate, in an unselected panel of patient derived xenograft models of breast cancer
Poster Board Number: 8
Session Category: Experimental and Molecular Therapeutics
Session Title: Antibody Drug Conjugates
Date/Time: Monday, April 11, 2022 at 1:30pm – 5:00pm CDT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 21

Poster Title: XMT-2056, a HER2-targeted Immunosynthen STING-agonist antibody-drug conjugate, binds a novel epitope of HER2 and shows increased anti-tumor activity in combination with trastuzumab and pertuzumab
Poster Board Number: 5
Session Category: Immunology
Session Title: Immunomodulatory Agents and Interventions 2
Date/Time: Tuesday, April 12, 2022 at 1:30pm – 5:00pm CDT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 37

Poster Title: Tumor cell-targeted STING-agonist antibody-drug conjugates achieve potential anti-tumor activity by delivering STING agonist specifically to tumor cells and FcγRI-expressing subset of myeloid cells
Poster Board Number: 15
Session Category: Immunology
Session Title: Innate Immunity to Cancer
Date/Time: Monday, April 11, 2022 at 1:30pm – 5:00pm CDT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 40

On April 5, 2022 Oncorus, Inc. (Nasdaq: ONCR), a viral immunotherapies company focused on driving innovation to transform outcomes for cancer patients, reported that it has entered into a loan and security agreement with K2 HealthVentures (K2HV), a healthcare focused specialty finance company (Press release, Oncorus, APR 5, 2022, View Source [SID1234611462]). Also today, Oncorus announced plans to relocate all its operations to its facility in Andover, Massachusetts in the fourth quarter of 2022, to allow research, process development and Good Manufacturing Practice (GMP)-compliant manufacturing to occur all in one facility. As a result of the term loan facility and operations relocation, as well as other initiatives to increase operational efficiency, Oncorus now expects its cash, cash equivalents and investments to fund its capital expenditures and operating expenses into early 2024.

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The term loan facility provides Oncorus with up to $45 million available in multiple tranches upon the achievement of certain time-based, clinical and regulatory milestones with the initial tranche of $20 million funded at closing. Oncorus intends to use the proceeds of the initial tranche of the loan facility to complete the buildout of its Andover facility, and to continue the advancement of its pipeline of next generation viral immunotherapies for cancer and lipid nanoparticle (LNP) technologies, including the filing of an investigational new drug application (IND) for its intravenously administered vRNA/LNP product candidate, ONCR-021, planned for mid-2023.

"Access to this additional capital from our partners at K2HV provides us with resources to aggressively pursue our strategic operational and manufacturing priorities, including the completion of construction of our manufacturing facility in Andover. This facility will play an integral role in helping us to rapidly advance our next generation viral immunotherapies for cancer patients derived from our HSV and selectively self-amplifying viral RNA (vRNA) platforms," said Ted Ashburn, M.D., Ph.D., President and Chief Executive Officer of Oncorus. "Coupled with this additional capital comes our decision to move all operations to our Andover facility by the fourth quarter of this year, providing us with increased synergies for our continued rapid growth and innovation, while extending our current cash runway into 2024. We are incredibly pleased to partner with the K2HV team and value their significant experience supporting successful biotechnology companies."

"We are excited to partner with Oncorus as they continue to build out their state-of-the-art manufacturing infrastructure and advance their dual-platform pipeline of product candidates targeting cancers with significant unmet need," added Anup Arora, Founding Managing Director & Chief Investment Officer at K2HV. "This financing is in line with our strategy of investing in innovative life sciences companies whose goals are to help improve outcomes for patients. We look forward to working with the Oncorus team and supporting their vision."

"The move to our Andover facility marks a significant turning point for Oncorus as we continue to work towards becoming a fully integrated leader in viral immunotherapies for cancer and LNP technologies," said Stephen W. Harbin, Chief Operating Officer and Chief of Staff of Oncorus. "By bringing our research, process development and GMP manufacturing teams to the same facility, we believe that we will be better positioned for rapid success while also providing an opportunity for strong collaboration and efficiency as we collectively work to achieve our milestones. The continued investment in manufacturing and building out our in-house LNP capabilities reflects our commitment to innovation and the value of our infrastructure."

Further information with respect to the loan and security agreement will be set forth in a Current Report on Form 8-K to be filed by Oncorus with the Securities and Exchange Commission on April 5, 2022.

On April 5, 2022 Sutro Biopharma, Inc. ("Sutro" or the "Company") (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 therapeutics, reported that Bill Newell, Chief Executive Officer, will present at the 21st Annual Needham Virtual Healthcare Conference on Thursday, April 14, 2022, at 3:00 p.m. ET / 12:00 p.m. PT (Press release, Sutro Biopharma, APR 5, 2022, View Source [SID1234611461]).

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The presentation will be accessible through the News & Events page of the Investor Relations section of the company’s website at www.sutrobio.com.

On April 5, 2022 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing innovative, targeted radiotherapeutics for rare and difficult-to-treat cancers, reported that it has expanded its partnership with Medidata, a Dassault Systèmes company (Press release, Cytori Therapeutics, APR 5, 2022, View Source [SID1234611460]).

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The goal of the expanded partnership is to speed enrollment, improve patient access to an innovative therapy and reduce clinical trial costs in Plus Therapeutics’ planned forthcoming Phase 2 registrational trial of Rhenium-186 NanoLiposome (186RNL) in recurrent glioblastoma (GBM). The partnership will utilize Medidata’s Synthetic Control Arm (SCA) platform that facilitates the use of historical clinical trial (HCT) data in a manner that historically has been favorably received by the U.S. Food and Drug Administration. The expanded partnership follows a successful preliminary assessment stage intended to determine project feasibility and probability of success.

"Synthetic control arms reduce the time and cost associated with complex clinical trials in rare diseases such as glioblastoma," said Norman LaFrance, M.D., Chief Medical Officer and SVP of Plus Therapeutics. "Plus has been quite impressed with Medidata’s team, capabilities and platform in the recently completed feasibility phase. Furthermore, the benefit is passed down to patients and their families, allowing for fewer patients to be exposed to placebos or existing standard-of-care treatments that might not be effective for them, offering them greater access to potentially life-extending therapies."

Medidata will provide the Company with a SCA based on a historical pool of anonymized HCT data to incorporate into Plus Therapeutics’ planned Phase 2 trial of 186RNL in recurrent GBM. SCAs are especially advantageous in indications such as recurrent GBM where the standard-of-care control treatment is considered undesirable by many patients and physicians.

About the Synthetic Control Arm

Medidata’s Synthetic Control Arm (SCA) – a type of external control – is formed by carefully selecting patients from Medidata’s extensive repository of historical clinical trials to match the baseline demographic and disease characteristics of the patients treated with the new investigational product. Case studies have shown that SCAs can effectively mimic a classic randomized control and, therefore, can be used to accurately interpret the treatment effects of an investigational product.

SCAs can help enhance the scientific validity of single-arm trials and, in certain indications, enhance randomized clinical trials to expose fewer prospective patients to control and/or ineffective or existing standard-of-care treatments that might not provide a benefit to the patient. This is done while still providing highly valid scientific evidence. These factors can influence a patient’s willingness to participate in a trial where there is a very poor prognosis and perceived inadequate standard of care.