On March 10, 2021 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported that preclinical anti-tumor efficacy in vivo data from its innate cell engager (ICE) AFM24 have been accepted for e-poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting I, being held on April 10-15 (Press release, Affimed, MAR 10, 2021, View Source [SID1234576521]).

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In addition, early data from a Phase 1 study evaluating AFM13 preloaded CAR-like cord blood-derived NK cells followed by weekly AFM13 monotherapy in patients with recurrent or refractory CD30-expressing lymphomas at The University of Texas MD Anderson Cancer Center will be presented by Katy Rezvani during a Major Symposium on April 13th.

Poster details:

Title: AFM24 is a novel, highly potent, tetravalent bispecific EGFR/CD16A-targeting Innate Cell Engager (ICE) designed for the treatment of EGFR-positive malignancies

Abstract: 1881

Authors: Jens Pahl, Gabriele Hintzen, Uwe Reusch, Torsten Haneke, Christian Breunig, Sheena Pinto, Cassandra Choe-Juliak, Andreas Harstrick, Wolfgang Fischer, Arndt Schottelius, Joachim Koch, Erich Rajkovic

Poster Release: The e-poster website will be launched on April 10, 2021. All e-posters will be available for browsing on this date. The poster will also be available on the Company’s website – www.affimed.com

Major Symposium Details:

Session Title: Engineering and Modulating Natural Killer (NK) Cells for Cancer Immunotherapy

Session Number: SY30

Talk: CAR-NK, a Drive to the Future of Cell Therapy

Speaker: Katy Rezvani, MD, PhD, Sally Copper Murray Endowed Chair in Cancer Research Professor of Medicine, Chief, Section of Cellular Therapy, Director for Translational Research Medical Director, SCT Laboratory and the GMP Laboratory, Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson

Moderated 30-minute Panel Session for Q&A Date: Tuesday, April 13, 1:30-2:00 pm ET

More details about the programs for the AACR (Free AACR Whitepaper) Virtual Annual Meetings are available online at www.aacr.org.

About AFM13

AFM13 is a first-in-class innate cell engager (ICE) that uniquely activates the innate immune system to destroy CD30-positive hematologic tumors. AFM13 induces specific and selective killing of CD30-positive tumor cells, leveraging the power of the innate immune system by engaging and activating natural killer (NK) cells and macrophages. AFM13 is Affimed’s most advanced ICE clinical program and is currently being evaluated as a monotherapy in a registration-directed trial in patients with relapsed/refractory peripheral T-cell lymphoma or transformed mycosis fungoides (REDIRECT). The study is actively recruiting, and additional details can be found at www.clinicaltrials.gov using the identifier NCT04101331.

In addition, Affimed is studying AFM13 in combination with cord blood-derived allogeneic NK cells in patients with recurrent or refractory CD30-positive Hodgkin or non-Hodgkin lymphomas. The investigator-sponsored Phase 1 study, conducted at the MD Anderson Cancer Center in Houston, is administering a CAR-like, stable complex of AFM13 pre-loaded cord blood-derived allogeneic NK cells. The study can be found at www.clinicaltrials.gov using the identifier NCT04074746.

About AFM24

AFM24 is a tetravalent, bispecific innate cell engager (ICE) that activates the innate immune system by binding to CD16A on innate immune cells and EGFR, a protein widely expressed on solid tumors, to kill cancer cells. Generated by Affimed’s fit-for-purpose ROCK platform, AFM24 represents a distinctive mechanism of action that uses EGFR as a docking site to engage innate immune cells for tumor cell killing through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.

Affimed is evaluating AFM24 as a monotherapy for patients with advanced EGFR-expressing solid malignancies whose disease has progressed after treatment with previous anticancer therapies. AFM24-101 is a first-in-human Phase 1/2a open-label, non-randomized, multi-center, multiple ascending dose escalation and expansion study and can be found at www.clinicaltrials.gov using the identifier NCT04259450. In addition, Affimed is planning to initiate further studies evaluating AFM24 in combination with adoptive NK cell transfer and in combination with atezolizumab.

On March 10, 2021 Molecular Partners AG (SIX: MOLN), a clinical-stage biotech company that is developing a new class of custom-built protein drugs known as DARPin therapeutics, reported the upcoming presentation of four posters with data supporting three of the company’s immunotherapy programs at the American Academy for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting running April 10-15, 2021 (Press release, Molecular Partners, MAR 10, 2021, View Source [SID1234576520]).

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The accepted research describes multiple aspects of validation for the unique mechanisms of these therapies in development for treating a wide range of tumor types.

Accepted abstract titles include:

MP0317 (targeting CD40 and FAP)
MP0317, a FAPxCD40 targeting multi-specific DARPin therapeutic, drives immune activation and leads to macrophage repolarization in vitro and ex vivo
T-cell engager programs
Novel multi-specific DARPin T-cell engager with an improved therapeutic window to overcome dose limiting toxicities in AML therapies.
A solution to T-cell engager toxicity: An anti-CD3 Prodrug DARPin (CD3-PDD) shows no toxicity, but potent anti-tumor activity in a humanized mouse model
Peptide-MHC program
Application of the DARPin technology for specific targeting of tumor-associated MHC class I: peptide complexes
For MP0317, the company’s multi-specific DARPin candidate targeting both FAP and CD40 to enable tumor-localized immune activation, the research describes how the candidate’s activation of immune cells in-vitro, as well as on human tumor samples, was dependent on the presence of the FAP protein, which is highly expressed in the stroma of a broad range of solid tumors. Furthermore, the research observed that immunosuppressive macrophages associated with tumor growth and spread were reverted by MP0317 into an anti-tumor phenotype. These data support MP0317’s potential to deliver tumor-localized CD40-mediated immune cell activation avoiding systemic toxicity seen in other agents. MP0317 is anticipated to begin clinical trials in the second half of 2021.

For the T-cell engager program, two accepted research abstracts detail the construction of next generation T-cell engager DARPin molecules designed to overcome the limited tumor specificity and the immune hyperstimulation associated with other T-cell engager approaches. By linking a T cell engaging CD3 DARPin binder to additional DARPin binder domains that optimally engage tumor-specific antigens in parallel, the company generated candidates that displayed strong in vitro potency, and low levels of cytokine release ex vivo – suggesting low systemic immune activation. Furthermore, an anti-CD3 Prodrug DARPin (CD3-PDD) was successfully designed to have its immunostimulatory effects inactivated by a linked ‘blocking’ DARPin domain, and become activated only in the tumor microenvironment, upon cleavage of the linker by tumor-associated proteases. In an in vivo humanized mouse tumor model, this candidate demonstrated anti-tumor activity and no toxicity when administered systemically. Together, the research supports Molecular Partners’ DARPin technology ability to control immunostimulation through a validated mechanism with a heightened level of precision relative to existing approaches.

Finally, for the peptide-MHC (pMHC) program, the research provides updates on the development of pMHC binders in the T cell engager format. The successful screening and engineering of the bispecific DARPin candidates (pMHC-CD3) achieved highly potent and specific T cell activation only in the presence of the target peptide, resulting in T-cell mediated tumor cell killing. A vast majority of tumor or viral antigens are presented as peptides on the cell surface by MHC molecules for immune cell recognition and have potential to be leveraged as versatile targets for immunomodulating therapeutics. However, to-date, antibody and T-cell receptor-based pMHC binders have been challenged by their low target abundance, weak affinity, cross-reactivity to other pMHCs, or challenging biochemical properties.

On March 10, 2021 Savara Inc. (Nasdaq: SVRA), an orphan lung disease company, reported that it intends to offer and sell, subject to market conditions, shares of its common stock in an underwritten public offering (Press release, Savara, MAR 10, 2021, View Source [SID1234576519]). In addition, Savara is offering to certain investors the right to purchase pre-funded warrants in lieu of common stock. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering. Savara intends to use the net proceeds from this offering for working capital to support operations, including but not limited to clinical development, manufacturing, regulatory, and commercial activities related to its molgramostim nebulizer solution (molgramostim, formerly referred to as Molgradex) in autoimmune pulmonary alveolar proteinosis (aPAP) program and the IMPALA 2 trial, and general and administrative expenses. In addition, Savara intends to grant the underwriters of the offering a 30-day option to purchase up to an additional 15% of the number of shares of common stock and pre-funded warrants offered in the public offering.

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Jefferies LLC and Piper Sandler are acting as joint book-running managers and representatives of the underwriters for the offering. Oppenheimer & Co. Inc. is acting as the lead manager and H.C. Wainwright & Co., LLC is acting as co-manager for the offering.

Savara intends to offer and sell these securities pursuant to its existing shelf registration statement (File No. 333-225994) filed with the Securities and Exchange Commission (SEC) on June 29, 2018 and declared effective on July 13, 2018. A preliminary prospectus supplement describing the terms of the offering has been filed with the SEC and forms a part of the effective registration statement. Copies of the preliminary prospectus supplement and accompanying prospectus relating to the offering may be obtained by contacting Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, or by telephone at (877) 547-6340, or by email at [email protected] or Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, Minnesota 55402, or by telephone at (800) 747-3924, or by email at [email protected]. An electronic copy of the preliminary prospectus supplement and accompanying prospectus relating to the offering will be available on the SEC website at www.sec.gov.

This press release does not constitute an offer to sell or the solicitation of offers to buy any securities of Savara, and shall not constitute an offer, solicitation, or sale of any security in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On March 10, 2021 Merus N.V. (Nasdaq: MRUS) ("Merus", "the Company", "we", or "our"), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported that Merus will present preclinical data from our zenocutuzumab and MCLA-129 programs in three poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2021 Annual Meeting being held virtually for two weeks, April 10-15, 2021 and May 17-21, 2021 (Press release, Merus, MAR 10, 2021, View Source [SID1234576518]).

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E-Poster Presentation:

Title: The HER2×HER3 bi-specific antibody zenocutuzumab is effective at blocking growth of tumors driven by NRG1 gene fusions
Abstract #: 956
Session Category: Experimental and Molecular Therapeutics
Session Title: Biological Therapeutic Agents

Title: Zenocutuzumab: An antibody that can overcome HER3 mediated HRG signaling in tumor cells by docking on HER2
Abstract Number: 957
Session Category: Experimental and Molecular Therapeutics
Session Title: Biological Therapeutic Agents

Title: The bispecific antibody MCLA-129 impairs NSCLC tumor growth by targeting EGFR and c-MET, inhibiting ligand-induced signaling and promoting ADCC and ADCP
Abstract Number: 952
Session Category: Experimental and Molecular Therapeutics
Session Title: Biological Therapeutic Agents

Abstracts are available on the AACR (Free AACR Whitepaper) annual meeting website.

The AACR (Free AACR Whitepaper) e-poster website will be launched on Saturday April 10, 2021. All e-posters will be available on this website from Saturday, April 10 to Monday, June 21, 2021. The posters will also be available on the Merus website as of Saturday, April 10, 2021.

About Zeno
Zeno is an antibody-dependent cell-mediated cytotoxicity (ADCC)-enhanced Biclonics that utilizes the Merus Dock & Block mechanism to inhibit the neuregulin/HER3 tumor-signaling pathway in solid tumors with NRG1 gene fusions (NRG1+). Through its unique mechanism of binding to HER2 and potently blocking the interaction of HER3 with its ligand NRG1 or NRG1-fusion proteins, Zeno has the potential to be particularly effective against NRG1+ cancers. In preclinical studies, Zeno also potently inhibits HER2/HER3 heterodimer formation and tumor growth in models harboring NRG1 fusions.

Learn more about Zeno Dock & Block at View Source

About MCLA-129
MCLA-129 is an ADCC-enhanced Biclonics that is designed to inhibit the EGFR and c-MET signaling pathways in solid tumors. Preclinical data has shown that MCLA-129 reverses resistance to tyrosine kinase resistant non-small cell lung cancer (NSCLC) cell lines resulting in tumor growth inhibition in xenograft models of NSCLC. MCLA-129 is designed to have two complementary mechanisms of action: blocking growth and survival pathways to stop tumor expansion and recruitment and enhancement of immune effector cells to eliminate the tumor.

On March 10, 2021 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of checkpoint antibodies, cell therapies, adjuvants, and vaccines designed to activate immune response to cancers and infections, reported that two abstracts on AGEN1181, Agenus’ Fc-enhanced next-generation anti-CTLA-4 antibody, were accepted for presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting from April 10 – 15, 2021 (Press release, Agenus, MAR 10, 2021, View Source [SID1234576517]).

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In a Phase 1/2 clinical study, AGEN1181 has shown responses in tumors previously unresponsive to immune therapies, including ovarian cancer and MSS endometrial and colorectal cancers. The AACR (Free AACR Whitepaper) presentation will cover the most up to date data. AGEN1181 is active even in patients with the low affinity FcγRIIIA allele, a genetic polymorphism which makes them generally unresponsive to first generation anti-CTLA-4. Further, AGEN1181 has demonstrated the ability to deplete intratumoral Tregs. Tregs are immunosuppressive T cells, and their depletion can allow for an improved antitumor immune response. Importantly, AGEN1181 is active without the neuroendocrine toxicities or hypophysitis observed with first generation agents.

The data to be presented at AACR (Free AACR Whitepaper) will showcase the optimal performance of AGEN1181 in preclinical models and in clinical trials. Preclinical data show that AGEN1181’s Fc enhancement allows it to engage the immune system even in cases of patients with the low affinity FcyRIIIA allele, which first-generation molecules do not do. These data also show that across all observed populations, AGEN1181 has increased efficacy over first-generation antibodies, and that combinations with multiple agents including checkpoint inhibitors such as anti-PD-1 and anti-TIGIT, iNKT-activating therapy, and adoptive T cell therapy, could further increase that efficacy.

In addition, clinical data to date provide evidence that these observations are being borne out in patients. Responses have been observed in patients with in the low-affinity FcyRIIIA allele. Further, AGEN1181 is the first anti-CTLA-4 to show intratumoral Treg depletion in the clinic.

AGEN1181 is currently advancing in a Phase 2 trial in colorectal cancer alone and in combination with balstilimab, Agenus’ anti-PD-1 antibody. As of February 9, Agenus has reported 6 confirmed objective clinical responses in its AGEN1181 Phase 1/2 trial and no complement-mediated toxicities.

Presentation Details:

Abstract title: Fc-enhanced anti-CTLA-4 antibody, AGEN1181: New mechanistic insights for potent antitumor immunity and combination potential in treatment-resistant solid tumors
Presenting author: Antoine Tanne, PhD

Abstract title: Characterization of the pharmacodynamic activity of AGEN1181, an Fc-enhanced CTLA-4 antibody, alone and in combination with the PD-1 antibody balstilimab
Presenting author: Irina Shapiro, PhD