On May 18, 2023 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage cell and gene therapy company advancing a new class of treatments for patients with cancer and rare diseases, today highlights its two oral and four poster presentations on the Company’s preclinical gene therapy programs and platforms at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 2023 Annual Meeting, being held at the Los Angeles Convention Center in Los Angeles and virtually May 16 – 20, 2023 (Press release, Poseida Therapeutics, May 18, 2023, View Source [SID1234631868]).

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"We are excited to highlight multiple advancements across our gene therapy programs and platform technologies at ASGCT (Free ASGCT Whitepaper), which underscore the significant progress our company has made in the past year," said Brent Warner, President, Gene Therapy at Poseida Therapeutics. "We are making encouraging progress with our P-OTC-101 program, where our hybrid LNP+AAV approach has shown its potential to deliver a functional cure for severe, pediatric-onset OTCD with a single dose. In addition, early preclinical data utilizing our Cas-CLOVER and non-viral piggyBac technologies continue to show great promise as we seek to unlock the potential of non-viral gene therapies for patients."

Oral Presentations

Title: Preclinical Proof-of-Concept: A Novel Hybrid Gene Therapy Approach to Treat Severe Early-Onset Ornithine Transcarbamylase Deficiency
Session Title: Metabolic, Storage, Endocrine, Liver and Gastrointestinal Diseases I
Presentation Time: Thursday, May 18, 2023, 2:30 – 2:45 PM PST
Location: Room 403 AB
Abstract Number: 127

Ornithine Transcarbamylase Deficiency (OTCD) is an X-linked urea cycle disorder that prevents the breakdown and excretion of ammonia, allowing it to rise to toxic levels and affect the central nervous system, leading to coma, seizures, brain damage, and death. Poseida has developed P-OTC-101, a liver directed gene therapy utilizing a hybrid lipid-nanoparticle (LNP) and adeno-associated virus (AAV) delivery system based on its piggyBac DNA insertion system to enable integration of the therapeutic human OTC gene into the genome. In this study, researchers demonstrated correction of severe OTCD following a single dose in a stringent mouse model of the disease. Researchers also reported preclinical pharmacology showing dose-response behavior as well as favorable translational safety and pharmacology in mice and non-human primates using this hybrid platform approach, which supports further development of P-OTC-101 towards evaluation in humans.

Title: Cas-CLOVER Technology Enables Precise Gene Editing and Site-Specific Transgene Insertion in Mouse Liver
Session Title: Gene Targeting and Gene Correction: Liver
Presentation Time: Thursday, May 18, 2023, 3:00 – 3:15 PM PST
Location: Room 515 AB
Abstract Number: 157

This presentation highlights the potential of Cas-CLOVER, Poseida’s high-fidelity, proprietary gene editing technology co-formulated with guide RNAs as a single LNP. Data demonstrated highly efficient editing and favorable tolerability in mice following a single dose of Cas-CLOVER with extremely low off-target editing in the liver. The study establishes proof-of-concept for knock-in of a transgene using Cas-CLOVER and a fully non-viral delivery system in mice and further supports the potential of this technology to develop effective therapies for rare diseases.

Poster Presentations

Title: Demonstration of Human Factor VIII Expression and Activity Following Single and Repeat Dosing of a Non-Viral Integrating Gene Therapy
Session Title: Wednesday Poster Session
Session Date/Time: Wednesday, May 17, 2023, 12:00 PM PST
Location: West Hall A
Abstract & Poster Board Number: 638

P-FVIII-101 is a fully non-viral liver-directed gene therapy combining Poseida’s proprietary piggyBac technology with nanoparticle delivery for the treatment of Hemophilia A. This study demonstrated the potential of P-FVIII-101 to produce durable human FVIII expression over six months in an adult mouse model of severe Hemophilia A following a single dose. The study also highlighted the potential of repeat dosing to achieve therapeutic levels of human FVIII activity. An integration site analysis revealed a favorable insertion profile and well-controlled integrated vector copy number. These data provide proof-of-principle evidence toward a potential functional cure for Hemophilia A.

Title: Development of a Novel Non-Viral Gene Therapy Platform
Session Title: Thursday Poster Session
Session Date/Time: Thursday, May 18, 2023, 12:00 PM PST
Location: West Hall A
Abstract & Poster Board Number: 945

The piggyBac DNA insertion system is a transposon-based gene therapy platform that enables stable integration of the therapeutic transgene into the genome, thereby offering the potential for durable and lifelong activity. This poster details formulation discovery work on an LNP comprising a novel degradable ionizable lipid with unique capabilities for efficient DNA delivery to the liver, as well as discovery and optimization of an LNP-based delivery system capable of co-encapsulating mRNA and DNA for delivery of piggyBac transposon system components.

Title: Editing of a γ-Globin (HBG1/HBG2) cis-Regulatory Element in Human Hematopoietic Stem and Progenitor Cells Using Cas-CLOVER Technology Reactivates Fetal Hemoglobin
Session Title: Thursday Poster Session
Session Date/Time: Thursday, May 18, 2023, 12:00 PM PST
Location: West Hall A
Abstract & Poster Board Number: 1212

This study demonstrates that high-fidelity Cas-CLOVER nuclease targeting of gamma globin genes provides efficient editing and reactivation of fetal hemoglobin expression. Cas-CLOVER-mediated gene editing of gamma globin genes was also shown to produce up to 70% positivity for fetal hemoglobin among differentiated red blood cells. Further, Cas-CLOVER-mediated gene editing did not adversely affect stem cell capabilities, including potential to produce the red blood cell lineage. These data support Cas-CLOVER editing of gamma globin genes as a potential therapeutic strategy for genetic diseases such as β-thalassemia and sickle cell disease.

Title: Development and Optimization of Novel Super piggyBac-Based Hybrid Gene Therapy Approach
Session Title: Friday Poster Session
Session Date/Time: Friday, May 19, 2023, 12:00 PM PST
Location: West Hall A
Abstract & Poster Board Number: 1318

This presentation describes the discovery and optimization of a novel LNP formulation suitable for delivery of Poseida’s super piggyBac transposase to the liver. In addition, these studies highlighted in vivo safety and pharmacology of Poseida’s lead LNP formulation in mice and non-human primates for use in liver-directed hybrid gene therapy applications. The presentation further characterizes the use of Poseida’s hybrid gene therapy platform in a mouse model of OTCD to achieve disease resolution at significantly lower doses of AAV. These data demonstrate the versatility of the piggyBac hybrid platform and its potential to achieve durable transgene expression when administered early in life.

On May 18, 2023 Myeloid Therapeutics, Inc. ("Myeloid"), a clinical stage mRNA-immunotherapy company, reported the completion of a $73 million financing led by Hatteras Investment Partners, with participation from new investors ARCH Venture Partners and Moore Strategic Ventures (Press release, Myeloid Therapeutics, May 18, 2023, View Source [SID1234631867]). All existing investors, including Newpath Partners, 8VC and Alexandria Venture Investments, also participated.

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"Myeloid continues to make significant progress across all aspects of our business. We are pioneering the convergence of immunology and RNA science to build a clinical-stage portfolio of products, starting with the significant unmet needs of cancer patients," said Daniel Getts, Ph.D., Chief Executive Officer of Myeloid. "We are pleased that such high-quality investors have joined with us to accelerate this effort."

Proceeds from the financing will support the continued clinical development of MT-101, Myeloid’s lead cell therapy program in Phase 1/2 for T cell lymphoma, and will accelerate the development of MT-302, a first-in-class TROP2-FcA mRNA-LNP product, into a Phase 1/2 study for TROP2-expressing tumors. Additional in vivo programming candidates are also advancing to the clinic.

Clay B. Thorp, General Partner at Hatteras, added, "Hatteras focuses on investments in cutting-edge companies that are disrupting the status quo and accelerating the pace of innovation. We are highly encouraged by the innovation, execution and clinical development progress demonstrated by Myeloid. We are proud to support this field-leading Company through its next phase of growth and are optimistic that these approaches will drive a meaningful clinical outcome for patients."

About MT-302

Emerging from the Company’s proprietary ATAK CAR receptor library, Myeloid’s novel in vivo engineering platform specifically targets and activates myeloid cells to elicit broader anti-tumor adaptive immunity. Through this approach, Myeloid demonstrates that delivery of lipid-nanoparticles (LNPs) encapsulating mRNA results in uptake and selective expression by myeloid cells in vivo, leading to potent tumor killing in multiple cold tumor models.

The Company’s lead in vivo program, MT-302, is a TROP2-targeting in vivo CAR designed for expression within the myeloid compartment. TROP2 is a tumor associated antigen expressed widely on epithelial tumors, including some of the most difficult to treat cancers. Treatment with MT-302 has demonstrated monotherapy activity in a TROP2/TNBC model, confirming the potency of programmed myeloid cells in the absence of T cells. Myeloid believes that MT-302 has significant advantages over TROP2-ADC approaches through its ability to engage the full immune response. In 2023, Myeloid expects to initiate a Phase 1/2 clinical study with MT-302 for patients with TROP2-expressing tumors.

About MT-101

MT-101 is the Company’s first autologous CAR monocyte. This candidate was derived from the Company’s proprietary ATAK platform and designed to harness the ability of myeloid cells to penetrate into tumors and promote broad anti-tumor activity. MT-101 targets CD5, a surface receptor that is present in greater than 75% of peripheral T cell lymphomas. To create MT-101, the patient’s cells are engineered ex vivo with the mRNA-strand coding for the CAR. The engineered cells are delivered back to the patient with a vein-to-vein time of eight days. The ATAK CAR is proprietary to Myeloid and manufactured using the Company’s patented processes.

The IMAGINE study (NCT05138458) is a Phase 1/2, multicenter, open-label, first-in-human, multiple ascending dose study to evaluate MT-101 in patients with refractory or relapsed PTCL and CTCL. The dose-escalation portion of this study, conducted with and without conditioning therapy, is open and enrolling patients.

RetroT

Retrotransposons are genetic elements that replicate through reverse transcription of an RNA transposition intermediate. Retrotransposons contribute to structural changes, and more importantly, to gene regulation. Myeloid’s RetroT technology relies on a single-strand mRNA to deliver genetic sequences and integration enzymes. This breakthrough technology offers the potential to deliver gene-sized pieces of DNA into the genome in a virus-free manner. The payload realizable with RetroT is larger than currently possible with all known existing gene editing technologies. As a result, the Company’s RetroT platform holds the potential to significantly expand the type and scope of genetic errors that can be reversed in situ. In March 2022, Myeloid entered into an exclusive option and research collaboration agreement with Prime Medicine, Inc. to develop and accelerate RetroT.

On May 18, 2023 ImaginAb, Inc., a global biotechnology company focused on the development of radiopharmaceuticals for the diagnosis and treatment of cancer, reported lead selection and progression to IND-enabling studies of IAB56, a minibody designed to target the αvβ6 integrin for use as Lu-177 radiopharmaceutical therapy in solid tumors. In parallel, the DLL3 targeting program, IAB57, will further assess several leads in the coming quarter prior to initiation of IND-enabling studies later in 2023 (Press release, ImaginAb, May 18, 2023, View Source [SID1234631866]). ImaginAb’s discovery team developed IAB56 and IAB57 at its Los Angeles R&D site via screening and selection of high affinity minibodies and cys-dibodies with demonstrated therapeutic efficacy in preclinical models.

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The αvβ6 integrin is a pan-cancer antigen implicated in a broad range of solid tumors including ovarian, pancreatic, breast, oral and liver cancer amongst others. The target shows expression which is highly specific to malignant diseases with very little or no expression in healthy tissues, making it an attractive candidate for targeted radiotherapy of solid cancers.

Delta-like ligand 3 (DLL3) is highly selective for SCLC and neuroendocrine tumors, with minimal to no expression in healthy tissues. Given the rapid recurrence of SCLC following existing therapeutic option, there remains a significant need to improve prognosis for patients suffering from this disease.

Ian Wilson, Chief Executive Officer of ImaginAb, said:

"The ImaginAb team has experience in the discovery, development, and manufacture of radiopharmaceuticals. Focusing our discovery team on the identification and progression of new radiopharmaceutical therapy agents based on our proprietary platform of biologics was a natural step for ImaginAb. We are excited to announce these new developments and look forward to sharing news on these and other candidate molecules as new milestones are met."

On May 18, 2023 OncoResponse, a clinical-stage biotech company advancing immunotherapies derived from the immune systems of Elite Cancer Responders, reported that it has been awarded a $13 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT) (Press release, OncoResponse, May 18, 2023, View Source [SID1234631865]). The Company concurrently raised $14 million in new funding from existing investors, led by RiverVest Venture Partners and including ARCH Venture Partners, Canaan Partners, 3B Future Health Fund, Bering Capital, Takeda Ventures, InterVest and others.

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The CPRIT award and investment will support the advancement of OR502, a best-in-class anti-LILRB2 antibody poised to move to IND and clinical studies. Funds from the existing syndicate will also support continued advancement of the Company’s lead immunotherapy candidate OR2805, a fully human monoclonal antibody identified from an Elite Responder using OncoResponse’s proprietary B-cell discovery platform. OR2805 is currently being evaluated in a Phase 1 clinical trial.

"We are thrilled to receive this recognition from CPRIT in supporting the potential of our immunotherapy candidate OR502. We greatly appreciate the additional support from our investors as we continue to make significant progress with our drug development efforts advancing immunotherapies derived from clues of Elite Responders," said Clifford Stocks, Chief Executive Officer of OncoResponse. "We are excited by the data generated to date supporting the ability of OR502 to modulate inhibitory macrophages in the tumor microenvironment and induce anti-tumor activity."

"We are pleased to support OncoResponse in their efforts to develop new and innovative immunotherapy treatments for cancer," said John McKearn, PhD, Managing Director of RiverVest Venture Partners. "The Company has made significant progress in building their pipeline and we look forward to further insights from future clinical studies."

On May 18, 2023 Navrogen, Inc., a biopharmaceutical company specialized in developing therapies for cancer and immune-related disorders, reported a publication describing new criteria for antibody-drug conjugate (ADC) development and preclinical efficacy of NAV-001 ADC against mesothelin-expressing tumor types (Press release, Navrogen, May 18, 2023, View Source [SID1234631864]). The publication is presented in the international peer-reviewed PLOS ONE journal and can be accessed at View Source

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NAV-001 ADC targets the cell surface mesothelin protein that is over-expressed by a number of cancers including triple negative breast, metastatic colorectal, non-small cell lung, pancreatic, ovarian and mesothelioma cancers. The publication highlights the negative impact on ADC efficacy caused by direct binding of tumor-produced Humoral Immuno-Oncology (HIO) factors to the ADC antibody component that in turn suppresses its ability to effectively internalize into antigen-expressing target cells thereby lowering its therapeutic efficacy. HIO factor binding to antibody is dependent on its three dimensional structure dictated by amino acids located in the antibody variable domain. Navrogen’s proprietary HIO factor screening platform enables the identification of antibodies that are naturally non-bound by HIO factors while its block-removed immunoglobulin technology (BRITE) platform enables engineering of HIO-refractory ADCs via replacement of amino acids responsible for HIO factor binding. NAV-001 was identified via HIO screening and contains a potent anti-cancer payload with topoisomerase II inhibitory activity. Preclinical studies using patient-derived xenograft (PDX) models have demonstrated NAV-001 single-dose efficacy across a wide array of mesothelin-positive cancers. Based on these data, NAV-001 is advancing towards clinical development as a single agent therapeutic against mesothelin expressing cancers along with a mesothelin diagnostic for patient pre-screening.

"NAV-001 is one of several assets that we have generated overcoming the negative impact that HIO factors can have on antibody-based therapeutics, including ADCs", said Dr. Nicholas Nicolaides, senior author. Implementing HIO screening into ADC development is another feature that may further improve the efficacy of this class of anti-cancer therapeutics".