On December 13, 2021 Boston Immune Technologies and Therapeutics, Inc. (BITT), a privately held developer of novel tumor necrosis factor (TNF) Superfamily antagonist antibodies, reported that the company has received a Small Business Innovation Research (SBIR) grant from the National Cancer Institute at the U.S. National Institutes of Health (Press release, BITT, DEC 13, 2021, View Source [SID1234596968]). The award is for a project titled "Preclinical Toxicology and Pharmacology Evaluation of a New TNFR2 Antagonistic Monoclonal Antibody for Cutaneous T Cell Lymphoma (CTCL) Therapy." The company also announced that Bruce Beutel, Ph.D., has joined BITT’s Board of Directors.

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"The SBIR funding will be used to complete the IND-enabling steps and initiate clinical trials of our anti-TNFR2 antibody, BIR2101," said Russell LaMontagne, Co-Founder and Chief Executive Officer of BITT. "We appreciate the recognition of our unique approach to TNFR2 antagonism and the importance of TNFR2 as novel target in cancer immunotherapy."

Dr. Beutel has over 25 years of leadership experience in drug discovery and business development. Before joining BITT, he was founding chief operating officer of Dewpoint and entrepreneur in residence at the LS Polaris Innovation Fund. His prior roles have also included chief business officer at SQZ Biotechnologies and executive director at Merck.

On December 13, 2021 Catamaran Bio, Inc., a biotechnology company developing off-the-shelf chimeric antigen receptor (CAR)-NK cell therapies to treat cancer, reported preclinical data that demonstrate key capabilities of its TAILWINDTM platform being applied to develop CAT-248, an allogeneic CD70-targeted CAR-NK cell therapy (Press release, Catamaran Bio, DEC 13, 2021, View Source [SID1234596967]). The data demonstrate successful engineering of a CD70 CAR-NK cell therapy that achieves cytotoxicity in vitro against various tumor cell lines. Using the integrated engineering and manufacturing capabilities of the TAILWIND platform, the data also show highly efficient non-viral delivery of a CAR targeting CD70 and knock out of endogenous CD70 in a single engineering step.

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The data support advancement of CAT-248, Catamaran’s co-lead CAR-NK cell therapy candidate, which is directed against CD70, a tumor antigen that is highly expressed on certain types of cancers including renal cell carcinoma, glioma, pancreatic cancer, and acute myeloid leukemia. The results were presented at the 63rd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) being held in Atlanta from December 11-14, 2021.

"CD70 is a compelling target in several high unmet need solid tumors and hematologic malignancies and we are excited to support the advancement of CAT-248 as an effective therapy for CD70 expressing cancers," said Alvin Shih, MD, MBA, Chief Executive Officer of Catamaran Bio. "These data further establish our TAILWIND platform as an industry-leading, highly versatile and scalable manufacturing platform for CAR-NK cell therapies, including complex products with multiple genome modifications."

"Our ASH (Free ASH Whitepaper) data demonstrate cutting-edge capabilities that are essential for both tumor-targeting design as well as scalable manufacturing of CAR-NK cell therapies," said Vipin Suri, PhD, MBA, Chief Scientific Officer of Catamaran Bio. "Notably, we have now demonstrated a novel single-step engineering approach for simultaneously using a non-viral transposon system for CAR delivery in combination with CRISPR editing for gene knockout. Using our TAILWIND platform, we effectively integrate all the necessary properties to position our CAR-NK cells as allogeneic, off-the-shelf therapies for multiple cancers, especially solid tumors."

Data presented in a poster titled, "Engineering CD70-Directed CAR-NK Cells for the Treatment of Hematological and Solid Malignancies," describe experiments showing key capabilities of the TAILWINDTM platform and characterization of the CD70-targeted CAR-NK cells. Highlights from the poster include:

CD70 was expressed across hematological and solid tumor malignancies but upregulated in activated peripheral blood NK cells.
Single-step, non-viral CAR delivery using the TcBusterTM Transposon System and CRISPR/Cas9 editing of NK cells resulted in more than 70% integration/expression of CD70 CAR and more than 80% knockout of endogenous CD70.
Activation of peripheral blood NK cells strongly upregulated CD70 expression, resulting in fratricide upon expression of CD70 directed CAR in these cells.
Knockout of endogenous CD70 enabled effective expansion of CD70 CAR-NK cells while maintaining innate cytotoxicity.
CAR-NK cells engineered with CD70 CAR and CRISPR/Cas9 knockout of endogenous CD70 were active against multiple CD70‑positive tumor lines.
The studies presented at ASH (Free ASH Whitepaper) are co-authored by Catamaran and its collaborators at the University of Minnesota. The poster presentation is available on Catamaran’s website.

On December 13, 2021 Zetagen Therapeutics, Inc., a private, clinical-stage, biopharmaceutical company dedicated to driving breakthrough innovation in the treatment of metastatic bone cancers and osteologic interventions, reported it has received a two year, $2 million USD grant from the National Cancer Institute of the National Institutes of Health (NIH) (Press release, Zetagen Therapeutics, DEC 13, 2021, View Source [SID1234596966]). The grant will be used for the Phase 2 clinical and commercial development of its ZetaMet technology. ZetaMet is a synthetic, small-molecule, inductive biologic technology being developed to target and resolve metastatic bone lesions while inhibiting future tumor growth and regenerating bone.

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"This support from the NCI marks a key milestone and will facilitate the continued development of ZetaMet for the use in treating metastasis in bone," said Bryan S. Margulies, PhD,chief scientific officer of Zetagen Therapeutics. "Preclinical trials have successfully demonstrated ZetaMet’s ability to resolve existing metastatic bone lesions, inhibit pain and stimulate targeted bone regeneration. If these results hold true in the next phase of study, ZetaMet could offer an entirely new treatment for patients living with certain late-stage cancers where present therapies do not offer desired results."

ZetaMet works through a mechanism of action (MOA) which is a novel and patented molecular pathway. The small molecule, precisely-dosed, delivered to the affected area through a proprietary drug-eluting carrier, stimulates stem cells, activating cells to grow healthy bone known as "osteoblasts", and inhibits cells associated with bone degradation called "osteoclasts".

Bone metastases are common among cancer patients and occur when cells from the primary cancerous tumor relocate to the bone. When these cancers relocate, they can cause changes to the bone, damaging it in a process called osteolysis. Osteolysis can cause small holes within the bone, weakening it and increasing the risk of breakage. These holes are called "lytic lesions." Among cancers which metastasize to bone, Breast and Prostate are most prevalent, amounting to approximately 70-percent of cases.1

"We know there are hundreds of thousands of patients living with late-stage cancers which involve painful, debilitating metastatic bone lesions," said Joe C. Loy, CEO of Zetagen Therapeutics. "This recognition from the NCI further reinforces our commitment to developing breakthrough therapies that will make a tangible difference in quality of life as they battle these devastating diseases."

Earlier this year, ZetaMet received Breakthrough Device designation from the Centers for Devices and Radiological Health (CDRH) of the U.S. Food and Drug Administration (FDA). The first human clinical trial using ZetaMet in Stage 4 breast cancer patients is being targeted for early 2022.

On December 13, 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 data from two of their Innate Cell Engager (ICE) programs at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH) (Free ASH Whitepaper) (Press release, Affimed, DEC 13, 2021, View Source [SID1234596964]). The poster presentations included preclinical proof-of-concept data on AFM28, for which Affimed recently revealed the target and indication. The program is in development for the treatment of Acute Myeloid Leukemia and other CD123+ hematologic malignancies. The second poster presentation provided data on the activity of AFM13 pre-complexed to NK cells after cryopreservation, demonstrating the potential to develop AFM13 as an off-the-shelf chimeric antigen receptor (CAR)-like NK cell product.

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Preclinical characterization of the ICE AFM28

The novel ICE AFM28 is designed to target CD16A on innate immune cells and CD123 on tumor cells in relapsed or refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). CD123 is almost universally expressed on leukemic blasts and leukemic stem cells (LSCs) and thereby represents a promising target in both indications.

The results revealed that target cell lysis via NK cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC), even at low CD123 expression, was more pronounced compared to conventional anti-CD123 antibodies. In addition, AFM28 showed a 100-fold more potent NK cell activation in an ex vivo analysis, compared to Fc-enhanced IgG1 antibodies. When compared with a CD123-targeting T cell-engaging bispecific antibody, AFM28 activity was associated with substantially lower levels of inflammatory cytokine release suggesting low risk of cytokine release syndrome. In support of these findings, administration of AFM28 to cynomolgus monkeys induced the effective depletion of CD123+ target cells and was well tolerated.

AFM28 is currently being prepared for clinical evaluation. The properties of the preclinical characterization make it an interesting candidate for combination approaches with allogeneic NK cell products.

"There is an urgent need for relapsed or refractory AML and MDS patients and targeting the innate immune system – either alone or in combination with adoptive NK cells – holds promise for these patients," said Dr. Arndt Schottelius, CSO of Affimed. "Our data suggests that AFM28 engages NK cells to lyse CD123-positive leukemic blasts and leukemic stem cells. This is a critical step in achieving long-lasting remissions."

Cryopreservation of NK cells pre-complexed with innate cell engagers (CAR-like NK cells)

Pre-complexing NK cells with the ICE AFM13 generates chimeric antigen receptor (CAR)-like NK cells. Our preclinical assays demonstrate that anti-tumor efficacy of AFM13 pre-complexed NK cells was comparable to NK cells that were combined, though not pre-complexed with AFM13. Furthermore, the data showed that tumor cell lysis was enhanced compared to a Fc-enhanced antibody approach.

Retaining biological activity and specificity after cryopreservation is a prerequisite to enable the development of pre-complexed off-the-shelf CAR-like NK cell products. Our results confirmed that the efficacy of tumor cell lysis by AFM13-pre-complexed NK cells, was virtually unaffected after one cycle of cryopreservation at -80°C.

"The data are the basis to develop an off-the-shelf precomplexed NK cell product of our ICE molecules and mark an important milestone," said Dr. Arndt Schottelius, CSO of Affimed. "This is especially encouraging as we recently announced very promising data of the Phase 1-2 study at The University of Texas MD Anderson Cancer Center that evaluates AFM13 pre-complexed with NK cells in patients with CD30-positive lymphomas revealing a 100% objective response rate in 13 patients who received the recommended phase 2 dose."

The poster will additionally be featured on December 15 at 5:00 pm ET in the virtual poster walk on Natural Killer Cell-Based Immunotherapy which can be accessed via the following link: View Source

The full posters are available on Affimed’s website under "Publications & Posters". For more details about the ASH (Free ASH Whitepaper) Virtual Annual Meeting please visit: View Source

About AFM28

AFM28, a tetravalent, bispecific CD123- and CD16A-binding ICE developed on Affimed’s ROCK platform, is designed to bring a new immunotherapeutic approach to patients with CD123+ myeloid malignancies, including acute myeloid leukemia and myelodysplastic syndrome (MDS). It engages NK cells to initiate tumor cell killing via antibody-dependent cellular cytotoxicity (ADCC), even at low CD123 expression levels. Clinical development is planned as both monotherapy and in combination with allogeneic NK cells in patients with relapsed/refractory CD123+ leukemias.

About AFM13

AFM13 is a first-in-class 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 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 (NCT04101331).

In addition, The University of Texas MD Anderson Cancer Center is studying AFM13 in an investigator-sponsored phase 1 trial in combination with cord blood-derived allogeneic NK cells in patients with relapsed/refractory CD30-positive lymphomas (NCT04074746).

On December 13, 2021 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported updated data from the ongoing Phase 1/2 clinical trial of MB-106, a CD20-targeted, autologous CAR T cell therapy for patients with relapsed or refractory B-cell non-Hodgkin lymphomas ("B-NHLs") and chronic lymphocytic leukemia ("CLL") (Press release, Mustang Bio, DEC 13, 2021, View Source [SID1234596962]). MB-106 is being developed in a collaboration between Mustang and Fred Hutchinson Cancer Research Center ("Fred Hutch").

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The data presented in a poster session at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting ("ASH2021") by Mazyar Shadman, M.D., M.P.H., Associate Professor, Clinical Research Division of Fred Hutch and a physician at Seattle Cancer Care Alliance, included efficacy and safety data from patients who were treated following a major cell manufacturing modification (n=20). Five dose levels were used during the study: 1 x 105, 3.3 x 105, 1 x 106, 3.3 x 106 and 1 x 107 cells/kg. Durable responses were observed in a wide range of hematologic malignancies including follicular lymphoma, diffuse large B-cell lymphoma, CLL, and Waldenstrom’s macroglobulinemia. An overall response rate ("ORR") of 95% and complete response ("CR") rate of 65% was observed in all patients across all dose levels. In patients with follicular lymphoma (n=15), the ORR was 93% and the CR rate was 73%. Robust CAR-T expansion and persistence was also observed. At the 28-day evaluation, a favorable safety profile was observed in all 20 patients, with no patients experiencing grade 3 or 4 cytokine release syndrome or immune effector cell‐associated neurotoxicity syndrome.

Mazyar Shadman, M.D., M.P.H., commented, "We are extremely pleased with the ongoing favorable safety profile and complete and durable responses with the current manufacturing process of MB-106, our third generation fully human CD20-targeted CAR T cell therapy for a mostly outpatient treatment of a wide range of relapsed or refractory hematologic malignancies. Given its safety and efficacy, CD20-targeted CAR T cell therapy has potential as an adoptive immunotherapy that could be utilized instead of, or in sequence with, CD19 CAR T cell therapy. Enrollment for this study remains robust for patients with CD20+ B-NHLs and CLL, including patients with prior CAR T treatment."

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "The updated data presented by Dr. Shadman at ASH (Free ASH Whitepaper)2021 expand on the compelling clinical activity of MB-106 in patients with relapsed or refractory B-cell hematologic malignancies. We are enthusiastic about the responses observed and look forward to the continued advancement of our CD20-targeted CAR T cell therapy program. We expect to enroll the first patient under Mustang’s MB-106 investigational new drug trial for patients with B-NHLs and CLL early next year."

Webinar
On Thursday, December 16, 2021, at 2:30 p.m. EST, Mustang will host a webinar with Dr. Shadman and colleague Brian Till, M.D., both of Fred Hutch and physicians at Seattle Cancer Care Alliance, to discuss the updated results from the ongoing Phase 1/2 clinical trial investigating the safety and efficacy of MB-106 CD20-targeted CAR T therapy for B-NHLs and CLL. Mustang’s management team will also provide more details on the planned MB-106 Phase 1/2 clinical trial to be conducted under Mustang’s Investigational New Drug ("IND") application. The U.S. Food and Drug Administration ("FDA") has accepted Mustang’s IND to initiate a multicenter Phase 1/2 clinical trial investigating the safety, tolerability and efficacy of MB-106 for relapsed or refractory B-NHLs and CLL. Following the formal presentations, the Mustang team, along with Drs. Till and Shadman, will be available for questions. To register for the webinar, please click here. An archived replay will be accessible on the Events page of the Investor Relations section of Mustang’s website: www.mustangbio.com for approximately 30 days following the call.

About MB-106 (CD20-targeted CAR T Cell Therapy)
CD20 is a membrane-embedded surface molecule which plays a role in the differentiation of B-cells into plasma cells. The CAR T was developed by Mustang’s research collaborator, Fred Hutch, in the laboratories of the late Oliver Press, M.D., Ph.D., and Brian Till, M.D., Associate Professor in the Clinical Research Division at Fred Hutch, and exclusively licensed to Mustang in 2017. MB-106 has been optimized as a third-generation CAR derived from a fully human antibody and is currently in a Phase 1/2 open-label, dose-escalation trial at Fred Hutch in patients with B-NHLs and CLL. Additional information on the trial can be found at View Source using the identifier NCT03277729.

Note: Scientists at Fred Hutch played a role in developing these discoveries, and Fred Hutch and certain of its scientists may benefit financially from this work in the future.