On April 25, 2022 BrickBio, the leader in RNA facilitated site- specific protein assembly, reported an invited poster at the annual meeting of the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Conference highlighting some of the results from its multi-year effort to develop the most efficacious therapeutic sites, inaccessible to other technologies, that the company incorporated into its Site Select Panel (Press release, BrickBio, APR 25, 2022, View Source [SID1234612934]). The panel uses the company’s powerful RNA engine to incorporate unnatural amino acids (UAAs) to produce 50 different homogenously conjugated antibodies in a matter of a few weeks.

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BrickBio has commercialized their flagship protein conjugation platform which leverages engineered RNA to introduce site-specific chemistries into any protein, enabling many applications through the same novel mechanism – such as homogenously conjugating two or more molecules to generate best-in-class therapeutics. Combined with the largest sets of compatible chemistries, BrickBio can incorporate and optimize any moiety ranging from oligonucleotides, LNAs, to complex hydrophobic payloads.

The pipeline candidate depicted in the poster (#3940), Next Generation Site-Specific ADCs targeting Breast and Gastric Cancer, highlighted the advantage of the powerful BrickADC platform towards breast & gastric cancer with improved efficacy, better safety, and overall lower dosages developed using the previously revealed Site-Select Panel. Identification of these optimal sites, which are inaccessible with other conjugation technologies, are currently being transferred between next-generation antibody scaffolds, such as bispecifics, nanobodies, or other fragments in BrickBio’s undisclosed internal and partnered pipeline.

BrickBio’s undisclosed pioneering efforts towards Protein Origami Therapeutics and Synthetic Virology were also highlighted, which leverage the same core technology that drive BrickADCs. Protein Origami enables the spatial orientation of multiple proteins into a multimeric complex, resulting in synergistic modalities that have yet to be explored due to the inability to generate such structures prior to BrickBio. In addition, the Synthetic Virology platform revolves around the retargeting of capsids via protein conjugation to engineer tropisms, improve safety, increase infectivity, and eliminate immunogenicity. BrickBio has produced stellar data in-vivo demonstrating conserved tropism, no immunogenicity, and 2X infectivity with improved AAV half-life.

BrickBio is continuing its partnership efforts from AACR (Free AACR Whitepaper) 2022 by meeting with potential collaborators for work on BrickADCs, Protein Origami Therapeutics, and modified AAV capsids.

"The BrickBio platform and processes have unleashed the full potential of the unnatural amino acid technology, enabling new therapeutic modalities, all linked by the same conjugation chemistries," said James Italia, VP of Commercial Development at BrickBio, "Specifically, the BrickADC platform highlights the unprecedented precision in our discovery engine. Our industry partners are adjusting their R&D directions since realizing they can engineer novel best-in-class therapeutics with BrickBio which they could not generate before." James concluded.

"BrickBio’s platform has the most diverse toolbox of engineered RNA and complementary chemistries, that have shown an immediate impact in producing improved, next generation, antibody drug conjugates, such as bispecific multi-site antibodies that have the ability to increase the drug to antibody ratio (DAR) while decreasing hydrophobicity," stated John Boyce, President, CEO, and Co-Founder of BrickBio, as well as Co-Founder of Tiger Gene, L.L.C. "The ability to modify therapeutic proteins extends beyond antibodies and protein-protein conjugates, but also to viral vectors such as modified AAVs with re-programmed tropism. These reprogrammed AAVs are being designed to provide a safe, tissue specific delivery vehicle that may re-ignite a number of gene therapy programs that have been stalled. BrickBio has delivered a near term solution to improve patient treatment through next generation ADCs, and is well positioned to usher in new era of gene therapy delivery vehicles," Boyce concluded.

On April 25, 2022 Medivir AB (Nasdaq Stockholm: MVIR) reported that the company will present at the Redeye Orphan Drugs Conference on April 27, 2022. CEO Jens Lindberg will present at 15.15 CET (Press release, Medivir, APR 25, 2022, View Source [SID1234612932]).

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On April 25, 2022 BioVaxys Technology Corp. (CSE: BIOV, FRA:5LB,OTCQB:BVAXF) ("BioVaxys" or "Company"), reported that it has entered into an agreement with the Deaconess Research Institute ("DRI") to supply BioVaxys with surgically debulked tumors from Stage III/Stage IV ovarian cancer patients undergoing treatment at Deaconess Health System ("Deaconess") (Press release, BioVaxys Technology, APR 25, 2022, View Source [SID1234612931]). DRI, based in Evansville, Indiana, is the clinical studies arm of Deaconess, a premier regional provider of health care services in the United States. Access to ovarian cancer tumor cells is a critical step enabling BioVaxys to validate the manufacturing process for BVX-0918, the Company’s autologous haptenized tumor cell vaccine for late-stage ovarian cancer.

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The standard of care for late-stage ovarian cancer often involves surgically debulking of the tumor mass. The debulked tumor cells will be used to test and validate the tumor collection protocol, cryopackaging, cryopreservation, and supply chain logistics for BVX-0918 bioproduction. Following shipment to BioElpida s.a. ("BioElpida"), the Company’s bioproduction partner in Lyon, France, the tumor cells will then be used for process testing and manufacturing "dry runs" of BVX-0918, a major step leading to the completion of Good Manufacturing Process ("GMP") production, a requirement for the planned Clinical Trial Application ("CTA") with the European Medicines Agency ("EMA"). BioVaxys, together with its EU partner, ProCare Health of Barcelona, Spain, is preparing to launch a Phase I clinical study for BVX-0918 later this year.

BioElpida developed various tests and validation procedures needed to support GMP manufacturing, such as sterility testing for transport, hapten fixation, and cryopreservation solutions, as well as antibody generation, bioburden screening of the haptens, and endotoxin assays; access to debulked tumor means that BioElpida will begin the final stages of the vaccine production protocol and GMP validation. BioVaxys and BioElpida have also designed and fabricated a specialized shipping package which would cryopreserve the tumor sample while in transit from any hospital site to the BioElpida site.

BioVaxys President & Chief Operating Officer Kenneth Kovan says, "Having complied with the regulatory oversight involved in obtaining waste tumor samples, BioVaxys is now able to provide BioElpida with the materials required for finalizing the vaccine production protocol and performing process validation in the lead up to our planned CTA submission to the European regulator."

BioVaxys’ vaccine platform is based on the established immunological concept that modifying surface proteins—whether they are viral or tumor—with haptens makes them more visible to the immune system. This process of haptenization "teaches" a patient’s immune system to recognize and make target proteins more "visible" as foreign, thereby stimulating a T-cell mediated immune response. BioVaxys’ cancer vaccines are created by extracting a patient’s own (autologous) cancer cells, chemically linking with a hapten, and re-injecting them into the patient to induce an immune response to proteins which are otherwise not immunogenic. Haptenization is a well-known and well-studied immunotherapeutic approach to cancer immunotherapy and has been clinically evaluated in both regional and disseminated metastatic tumors.

A first generation single-hapten vaccine invented by BioVaxys Co-Founder and Chief Medical Officer David Berd, MD, achieved positive immunological and clinical results in Phase I and Phase II human trials in over 600 patients with different tumor types, as well as having no observed toxicity in years of clinical study. These studies were conducted under an FDA-reviewed IND. A first generation autologous, haptenized vaccine was also tested by Dr. Berd in women with advanced ovarian cancer who had ceased to respond to conventional chemotherapy. The results were encouraging: In 24 patients, the median overall survival was 25.4 months with a range of 4.5-57.4 months; 8 patients survived for more than 2 years. BioVaxys has enhanced the first-generation approach by utilizing two haptens ("bi-haptenization"), which the Company believes will yield superior results.

On April 25, 2022 Orca Bio, a clinical-stage biotechnology company developing purified, high-precision cell therapies for the treatment of cancer, genetic blood disorders and autoimmune diseases, reported that positive new data were presented at the 2022 Transplantation & Cellular Therapy ASTCT and CIBMTR Tandem Meetings in Salt Lake City, Utah (Press release, Orca Bio, APR 25, 2022, View Source [SID1234612929]).

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The new data on Orca Bio’s lead investigational high-precision cell therapy, Orca-T, include updated results from 137 patients with hematologic malignancies, which continued to show an increase in overall survival rates and a reduction of acute and chronic graft versus host disease (GvHD) compared to standard of care; positive outcomes in a subset of patients with myelofibrosis who received Orca-T; and new analyses demonstrating Orca Bio’s manufacturing platform is reliable, robust and scalable.

"These data from an expanded group of patients are very encouraging and demonstrate that Orca-T appears to improve survival while reducing GvHD. This could be a compelling option for patients battling serious hematological malignancies who currently face devastating transplant-related risks," said Everett Meyer, M.D., Ph.D., primary investigator. "These results, combined with the reliable and centralized Orca-T manufacturing, could potentially transform treatment options for patients and physicians."

Orca Bio presented pooled data from 137 patients in the single-center Phase 2 and multi-center Phase 1b trials of Orca-T with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndromes (MDS), with at least 100 days of follow-up and a median of 341 days. For comparison purposes, an independent CIBMTR-based control arm was identified, consisting of similar patients with hematologic malignancies who received a standard of care allogeneic hematopoietic stem cell transplant ("alloHSCT") over a similar timeframe. Results demonstrated that:

Rates of moderate-to-severe chronic GvHD were low among Orca-T recipients, occurring in only 5% of patients at one year compared to 38% who received a standard alloHSCT.
GvHD-free, relapse-free survival (GRFS) was 71% at one year for Orca-T patients compared to 21% in the CIBMTR-based control arm.
The overall survival for patients who received Orca-T was 90% at one year compared to 68% in the CIBMTR-based control arm.
Additionally, Orca Bio presented findings from a manufacturing reliability analysis of 100 Orca-T products in the Phase 1b trial. All investigational cell therapies were manufactured at Orca Bio’s cGMP facility in Sacramento, CA, and transplant centers and donor sites were located across the U.S. All products were successfully delivered and infused to patients within 72 hours or less.

"We produce a unique batch of drug for each patient who receives an Orca-T product, and this drug is made up of fresh, living cells that need to be infused on an extremely rapid timeline," said Nate Fernhoff, Ph.D., co-founder and chief scientific officer at Orca Bio. "Reliable and scalable manufacturing have been integral to the development of our therapies since day one. These results not only show that Orca-T continues to reduce GvHD and improve survival rates over time, but that we have maintained the ability to reliably manufacture, deliver and infuse all patients in a timely manner regardless of donor and patient location. This is an important indication of our ability to potentially deliver this therapy urgently and seamlessly to patients in need."

In a separate poster, Orca Bio presented updated data on the treatment impact of Orca-T in 12 patients with myelofibrosis compared to nine patients who received a standard of care alloHSCT. Orca-T recipients had lower incidence of acute and chronic GvHD (33% with Orca-T versus 100% with alloHSCT) and the data suggest Orca-T was well-tolerated. Treatment with Orca-T resulted in engraftment with regression of marrow fibrosis, indicating potential efficacy for the treatment of myelofibrosis.

Based on the favorable results of the Phase 1b and 2 clinical trials, a randomized registrational Phase 3 trial evaluating Orca-T against standard of care alloHSCT, named Precision-T, is now open. More details will be announced in the coming weeks.

Links to the abstracts follow:

Title: Orca-T Demonstrates Encouraging Overall Survival, Gvhd Reduction, and Tolerability in Patients with Hematologic Malignancies
Poster Number: 412

Title: Outcomes for Myelofibrosis Patients Following Myeloablative Allogeneic Stem Cell Transplantation Using the Orca-T Graft from HLA-Matched Related and Unrelated Donors
Poster Number: 413

Title: Manufacture and Distribution of High-Precision Orca-T Is Reliable, Robust, and Scalable
Poster Number: 415

About Orca-T
Orca-T is an investigational high-precision allogeneic cellular therapy consisting of infusions containing regulatory T-cells, conventional T-cells and CD34+ stem cells derived from peripheral blood from either related or unrelated matched donors. Orca-T has received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration and is being studied to treat multiple hematologic malignancies.

On April 25, 2022 Quantum Leap Healthcare Collaborative (Quantum Leap) and Ambrx Biopharma Inc., or Ambrx, (NYSE: AMAM), a clinical stage biopharmaceutical company using an expanded genetic code technology platform to create Engineered Precision Biologics, reported the selection of Ambrx’s antibody drug conjugate (ADC) ARX788 for a new investigational treatment arm in the I-SPY 2.2 TRIAL for the treatment of HER2-positive breast cancer in the neoadjuvant setting (Press release, Ambrx, APR 25, 2022, View Source [SID1234612928]). Sponsored by Quantum Leap, the I-SPY 2.2 TRIAL is a continuation of the I-SPY 2 TRIAL that seeks to create personalized treatments by adapting therapies for each patient to optimize the clinical outcome.

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"We are particularly excited about this collaboration," stated Dr. Laura J. Esserman, MD, MBA, Director of the Breast Care Center at the UCSF Helen Diller Family Comprehensive Cancer Center, and Principal Investigator of I-SPY Family of Trials. "We hope this will usher in an era of more targeted, effective and less toxic therapies for people with HER2-positive breast cancers, leveraging decades of investment in science and drug development, and delivering better treatment to patients when they need it most. This is the right drug, for the right patient at the right time."

I-SPY 2.2 is an adaptive Phase 2 clinical trial that evaluates emerging targeted agents, allowing those agents to either be combined with less toxic chemotherapeutic regimens or to replace cytotoxic chemotherapy entirely. ARX788 will be evaluated as a monotherapy, and in combination with the PD-1 targeting checkpoint inhibitor cemiplimab, in HER2-positive early-stage breast cancer in the neoadjuvant setting. Ambrx anticipates the ARX788 arms to begin enrolling patients in May 2022.

Quantum Leap, sponsor of the I-SPY 2.2 TRIAL, leads a pre-competitive consortium that includes the U.S. Food & Drug Administration (FDA), industry, patient advocates, philanthropic sponsors, and clinicians from more than 16 major U.S. cancer research centers.

"I am thrilled that Quantum Leap has selected Ambrx’s antibody drug conjugate, ARX788, to be evaluated in the I-SPY 2.2 TRIAL," said Feng Tian, Ph.D., Chairman of the Board, President, and CEO of Ambrx. "We are encouraged by the favorable anti-tumor activity and safety profile of ARX788 for the treatment of early-stage breast cancer. It may provide a less toxic treatment option for patients through the precision conjugation of cytotoxic payloads targeting HER2 receptors. I look forward to collaborating with Quantum Leap and exploring the potential of our antibody drug conjugate in enabling effective chemo-free therapeutic treatments to patients."

ARX788 is an anti-HER2 antibody drug conjugate (ADC) that is being studied broadly in breast cancer, gastric/GEJ cancer and other solid tumors. ARX788 is a homogeneous and highly stable ADC that maximizes potential anti-tumor activity by optimizing the number and position of its payloads and the chemical bonds that conjugate the payloads to the antibody. The United States Food and Drug Administration (FDA) has granted ARX788 the Fast Track Designation for the treatment of HER2-positive metastatic breast cancer.