On January 4, 2024 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, reported recent progress across the company’s cell and gene therapy portfolio and provided updates on anticipated upcoming milestones (Press release, Poseida Therapeutics, JAN 4, 2024, View Source [SID1234638994]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In 2023, we made significant progress in delivering on the promise of our pipeline of allogeneic cell therapies through both substantial manufacturing advancements and compelling clinical data. At the ASH (Free ASH Whitepaper) Annual Meeting, we were thrilled to highlight the ability of P-BCMA-ALLO1, our TSCM-rich CAR-T therapy for multiple myeloma, to offer a compelling emerging efficacy and safety profile that we believe will be competitive with autologous cell therapies and bispecific antibodies, and to treat patients without lengthy waiting times," said Kristin Yarema, Ph.D., President and Chief Executive Officer of the Company. "In parallel, we expanded our partnership with Roche, accelerating the expected timing of achievement and increasing the certainty of certain milestones as well as advancing programs at all stages in the Roche collaboration. Notably, we cleared the IND for P-CD19CD20-ALLO1, which we believe is the first known dual allogeneic CAR-T directed against CD19 and CD20. In our non-viral gene therapy portfolio, we are advancing P-FVIII-101 as a potentially durable treatment for Hemophilia A and believe that the recent preclinical data presented at ASH (Free ASH Whitepaper) continue to support our liver-targeted non-viral delivery platform. Together with our strong financial position and bolstered by our robust business development and partnership activity, we believe we are well positioned for success in 2024."

"As we work to build on this momentum in 2024, we plan to report interim Phase 1 data in both our BCMA and MUC1C programs as well as dose the first patient in our allogeneic CD19CD20 dual CAR program targeting B-cell malignancies, which is partnered with Roche. We also expect to advance IND-enabling studies directed toward our wholly-owned allogeneic PSMA program in prostate cancer. In our gene therapy portfolio, we look forward to providing a comprehensive strategic update at our upcoming gene therapy-specific R&D Day in April, as we continue advancing our non-viral DNA delivery platform to unlock potential for genetic diseases. We believe we are entering a new era of cell and gene therapies, and I am thrilled to step into the role of President and CEO of Poseida at this transformative moment."

Program Highlights

Cell Therapy Programs

BCMA Program
P-BCMA-ALLO1 is a potential first-in-class allogeneic, TSCM-rich CAR-T product candidate being developed to target B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma (R/R MM) in partnership with Roche. The Company is currently evaluating P-BCMA-ALLO1 in a Phase 1 clinical trial and recently shared positive early safety and preliminary efficacy data at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in December 2023.

Data highlighted at the meeting showed that P-BCMA-ALLO1 was a well-tolerated off-the-shelf therapy with a favorable emerging safety profile, delivered to 100% of patients in the intent-to-treat population with no use of bridging chemotherapy or other anti-myeloma bridging therapies. There were no cases of GvHD or dose-limiting toxicities and low incidences of CRS and neurotoxicity observed (all ≤ Grade 2). The data showed an 82% overall response rate (ORR) and deep clinical responses, including stringent complete responses (sCRs) in MRD-negative patients, from the off-the-shelf, allogeneic BCMA-targeted CAR-T in heavily pretreated patients in study arms receiving adequate lymphodepletion. Of those patients, a 100% ORR was seen in patients who were not previously treated with a BCMA-targeted bispecific T cell-engaging antibody. The median time from study enrollment to start of lymphodepletion chemotherapy was 1 day and was 7 days to P-BCMA-ALLO1 infusion. Preliminary data show allogeneic TSCM-rich CAR-T cells trafficking to bone marrow, differentiating to cell-killing effector T cells and persisting at least 6 weeks after treatment, which supports the hypothesis of cell persistence at tumor-relevant sites. At the time of data cutoff, 8 of 9 responding patients were still in clinical response.

In 2024, Poseida plans to continue development of P-BCMA-ALLO1 in partnership with Roche. This includes continuing the strong enrollment in the Phase 1 study, refinement of dosing regimen for both cell dose and lymphodepletion chemotherapy, sharing additional details on clinical trial expansion strategies and continuing product supply efforts. The Company plans to present additional clinical data updates for P-BCMA-ALLO1 at scientific meetings in 2024, subject to coordination with Roche.

CD19CD20 Program
P-CD19CD20-ALLO1 is an allogeneic, TSCM-rich CAR-T product being developed to target B-cell malignancies in partnership with Roche. P-CD19CD20-ALLO1 is the Company’s first dual CAR program and contains two fully functional CAR molecules to target cells that express either CD19 or CD20 or both. The Company believes P-CD19CD20-ALLO1 is the first known dual allogeneic CAR-T directed against CD19 and CD20 to receive IND clearance from the FDA. The Company expects to dose the first patient in the Phase 1 trial of P-CD19CD20-ALLO1 for B-cell malignancies in early 2024 and provide a data update later in the year, subject to coordination with Roche.

MUC1C Program
P-MUC1C-ALLO1 is an allogeneic, TSCM-rich CAR-T product candidate targeting the C-terminal domain of the mucin-1 protein (MUC1C), which is prevalent in solid tumors of epithelial origin, including breast, ovarian, and multiple other cancers. The Company is currently evaluating P-MUC1C-ALLO1 in a Phase 1 clinical trial with a basket study design. Building on learnings from the allogeneic BCMA CAR-T program, the Company is evaluating multiple dosing strategies, including higher lymphodepletion, cell dose, and schedule in its MUC1C program. Poseida plans to provide a data update at a scientific meeting in the first half of 2024.

PSMA Program
P-PSMA-ALLO1 is an allogeneic CAR-T product candidate targeting prostate-specific membrane antigen, or PSMA, to treat prostate cancer. This allogeneic program utilizes VH-based binding technology, similar to the approach used in the Company’s P-BCMA-ALLO1 program, but targeting PSMA. When compared to the previous autologous PSMA program that used a Centyrin binder, in preclinical models, enhanced anti-tumor activity was observed using this newer binder. Based upon progress and learnings from its autologous P-PSMA-101-001 clinical trial and across its allogenic platform, the Company plans to advance IND-enabling work for P-PSMA-ALLO1 in 2024.

Early Stage Research
The Company plans to continue early pipeline research activities and advance IND-enabling work for other allogeneic pipeline programs, including exploring opportunities in autoimmune disease.

Gene Therapy Programs

At its Gene Therapy R&D Day event in April 2024, the Company plans to share updates on its programs and outcomes from its strategic review process.

FVIII Program
The Company is advancing its P-FVIII-101 preclinical program, a fully non-viral liver-directed gene therapy combining Poseida’s proprietary piggyBac DNA Delivery System with nanoparticle delivery for the treatment of Hemophilia A. The Company recently presented preclinical data from this program at the ASH (Free ASH Whitepaper) Annual Meeting in December 2023, demonstrating the capabilities of the piggyBac DNA insertion system and non-viral approach in providing stable Factor VIII transgene expression, along with the potential for redosing. The P-FVIII-101 program is among the programs advanced through the Company’s former partnership with Takeda and Poseida received full rights back after Takeda’s change in strategy away from gene therapy and rare disease.

OTC Program
P-OTC-101 is a liver-directed gene therapy for the treatment of urea cycle disease caused by congenital mutations in the ornithine transcarbamylase (OTC) gene. The Company is developing the P-OTC-101 program utilizing a hybrid delivery system (AAV+LNP) and working on an updated timeline for the program. P-OTC-101 received orphan drug designation from the FDA in July 2023.

PAH Program
P-PAH-101 is a liver-directed gene therapy for the treatment of Phenylketonuria (PKU), an inherited genetic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene resulting in a buildup of phenylalanine in the body. The Company is developing P-PAH-101 program utilizing a hybrid system (AAV+LNP) and is currently in preclinical development.

Other Business Highlights

Fully Operationalized Internal Manufacturing Capabilities
Poseida has made substantial advancements in its allogeneic cell therapy manufacturing platform and capabilities. In 2023, Poseida established a fully internal clinical manufacturing capability which is now supplying all GMP products for all of its clinical trials across three programs. In addition, the Company has achieved yield improvements through optimization of unit operations, as described at the CAR-TCR Summit in September 2023, capable of delivering cell yields supporting up to 100+ doses per manufacturing run depending upon cell dose.

In 2024, the Company plans to continue to invest in its allogeneic platform for TSCM-rich CAR-T, including proprietary non-viral technologies, and will continue to refine and improve its manufacturing processes in ways that will potentially further increase product yield generally.

Partnerships and Collaborations
In August 2023 the Company announced a $50 million strategic investment by Astellas and granted Astellas certain strategic rights, further validating Poseida’s suite of genetic engineering technologies and its allogeneic T cell platform.

Poseida continues to develop allogeneic CAR-T therapies targeting hematological malignancies in partnership with Roche. The Company announced in November 2023 that, based upon substantial progress in its P-BCMA-ALLO1 and P-CD19CD20-ALLO1 programs, certain payments as well as the expected timing of achievement of upcoming milestones in programs have been accelerated to reflect progress in the programs and better align with expected upcoming further clinical developments and manufacturing needs and timelines. As a result of this progress, the Company expects to receive certain payments sooner and/or with more certainty than originally anticipated.

The Company continues to explore potential strategic and business development options for its technology platforms and gene therapy programs, as well as other potential opportunities in cell therapy.

Poseida R&D Days
In recognition of its continued development and growth, and to highlight its proprietary platform technologies and preclinical research in 2024, the Company plans to hold two R&D Days focusing on gene therapy and cell therapy respectively.

Poseida will hold an R&D Day focusing on gene therapy on April 17, 2024, when the Company plans to provide an update on its strategic review of its gene therapy and gene editing programs, as well as updates on its pipeline and focus areas. An R&D Day focusing on cell therapy will be hosted in the second half of 2024.

Organization

Kristin Yarema, Ph.D., has been appointed to the Company’s Board of Directors, effective January 1st, 2024.

Cash Position and Runway

As previously announced, Poseida expects that its cash, cash equivalents and short-term investments together with the remaining near-term milestones and other payments from Roche and Astellas will be sufficient to fund operations into the second half of 2025. This cash runway reflects financial prudence but has mainly been driven through business development and partnership activity, for which Poseida continues to be well positioned.

On January 4, 2024 Medivir AB (Nasdaq Stockholm: MVIR), a pharmaceutical company focused on developing innovative treatments for cancer in areas of high unmet medical need, reported that Medivir’s licensee, Tango Therapeutics (NASDAQ: TNGX; Tango), has dosed the first patient with TNG348, a novel USP1 inhibitor (Press release, Tango Therapeutics, JAN 4, 2024, View Source [SID1234638993]). Tango received U.S. Food and Drug Administration clearance on its Investigational New Drug application for TNG348 in September 2023.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

TNG348 is a novel USP1 (ubiquitin-specific protease 1) inhibitor for the treatment of BRCA1/2-mutant and other homologous recombination deficiency (HRD)+ cancers. HRD+ cancers, including BRCA1/2 mutations, represent up to 50% of ovarian cancers, 25% of breast cancers, 10% of prostate cancers and 5% of pancreatic cancers. Tango is developing TNG348 from the preclinical USP1 program licensed from Medivir in 2020.

In the study, TNG348 will be evaluated both as single agent and in combination with olaparib (PARP-inhibitor) in patients with BRCA1/2-mutant and other HRD+ cancers. Preclinical data has shown synergistic effect with PARP inhibitors in PARP naïve models, including models with resistance to PARP inhibitors.

– "The preclinical data generated by Tango for TNG348 is promising and dosing the first patient in a clinical study is encouraging for patients with HRD+ cancers. The efforts undertaken by Tango to develop TNG348 into a clinical-staged drug are impressive and we will continue to follow the clinical development of TNG348 with great anticipation," says Jens Lindberg, CEO of Medivir.

Under the licensing agreement, Medivir is entitled to multiple development and commercial milestone payments as well as royalties on future sales. Dosing the first patient in a clinical trial triggers a milestone payment.

On January 4, 2024 Boehringer Ingelheim and 3T Biosciences ("3T") reported they have entered into a new strategic collaboration and licensing agreement focused on discovering and developing next-generation life-changing cancer immunotherapies (Press release, Boehringer Ingelheim, JAN 4, 2024, View Source [SID1234638992]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Despite the significant transformation of the cancer treatment landscape by immunotherapies, sustained remission only occurs in 15-20% of all cases of cancer. Boehringer Ingelheim is on a mission to considerably increase this rate by utilizing complementary immuno-oncology platforms such as T-Cell Engagers (TcEs), oncolytic viruses and cancer vaccines to extend the benefits of immunotherapy to more patients in need.

This second research partnership with 3T builds on the successful completion of the initial research partnership announced last year by the two companies. It brings together 3T’s best-in-class 3T-TRACE (T-Cell Receptor Antigen and Cross-Reactivity Engine) discovery platform with Boehringer Ingelheim’s commitment to develop first-in-class immuno-oncology treatments that boost the immune system’s ability to recognize, attack and kill tumors.

"At Boehringer Ingelheim, we are committed to transforming patients’ lives. The initial success of our work with 3T gives us confidence that together we can and will expand and accelerate our pipeline of first-in-class T-cell based anti-cancer therapies," said Lamine Mbow, Ph.D., Global Head of Cancer Immunology and Immune Modulation, Boehringer Ingelheim.

"The work we have done with Boehringer Ingelheim over the past year provides a higher degree of validation of our 3T-TRACE discovery platform," said Stefan J. Scherer, M.D., Ph.D., president and CEO of 3T Biosciences. "Based on the success of this initial work, we will now go broader and deeper into other cancers."

Under the agreement, Boehringer Ingelheim will provide patient-derived T-cell receptor (TCR) data to fuel 3T’s target discovery efforts to identify cognate antigens using its 3T TRACE discovery platform. 3T will receive an upfront payment and research and development support, and is eligible for discovery, preclinical, clinical, regulatory, and commercial milestones for both agreements totaling $538.5 million in addition to royalties on future Boehringer Ingelheim product sales. Boehringer Ingelheim is eligible to receive royalties on future product sales by 3T Biosciences arising from the agreement.

On January 4, 2024 Avenzo Therapeutics, Inc. (Avenzo), a clinical-stage biotechnology company developing next generation oncology therapeutics, reported that it has entered into an exclusive licensing agreement with Allorion Therapeutics Inc. (Allorion) to develop and commercialize AVZO-021 (formerly ARTS-021), a potentially best-in-class cyclin-dependent kinase 2 (CDK2) selective inhibitor globally (excluding Greater China) (Press release, Avenzo Therapeutics, JAN 4, 2024, View Source [SID1234638991]). As part of the agreement, Avenzo also receives an exclusive option for an additional preclinical program planned for IND submission in early 2025.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

CDK2 has emerged as a promising target given its role as a resistance mechanism to approved CDK4/6 therapies in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, and given its role as an oncogene in many cyclin E1 (CCNE1) amplified cancers. Avenzo will leverage its internal drug development expertise to advance AVZO-021, which is currently being studied in a Phase 1 clinical trial across multiple sites in the U.S. for the treatment of HR+/HER2- metastatic breast cancer and other advanced solid tumors.

"With this agreement, we have laid the foundation for our potentially best-in-class oncology pipeline," said Athena Countouriotis, M.D., co-founder, president and CEO of Avenzo. "Patients with HR+/HER2- metastatic breast cancer continue to have limited therapeutic options, and we believe AVZO-021 may provide patients with a new treatment option both as a single agent and in multiple combinations. We are excited to advance the ongoing Phase 1 clinical study (NCT05867251), and to partner with the Allorion team to advance the program globally."

Under the terms of the license agreement, Allorion will receive an upfront payment of $40 million and be eligible to receive additional payments based on achievement of certain development, regulatory and commercial milestones and tiered royalties on net sales by Avenzo. Potential payments for both programs may total more than $1 billion.

"We developed AVZO-021 as a potential best-in-class CDK2-selective inhibitor to address an area of unmet medical need," said Peter Ding, co-founder and CEO of Allorion. "The Avenzo team has a proven track record and deep expertise in developing and advancing next-generation oncology therapies. We are delighted to partner with Avenzo to drive innovation and transform the treatment landscape for cancer patients."

"AVZO-021 is a highly potent and selective CDK2 inhibitor for the treatment of HR+/HER2- breast cancer and CCNE1-amplified cancers," said Afshin Dowlati, M.D., Professor of Medicine and Oncology at University Hospitals Seidman Cancer Center and Case Western Reserve, and Director of the Early Phase Therapeutics Program. "I look forward to working with Avenzo as they continue to develop this therapy that has the potential to provide a new treatment option to patients fighting cancer."

In preclinical studies, AVZO-021 exhibited nanomolar potency against CDK2 while sparing other CDKs with high selectivity over CDK1, a key driver of toxicity. In addition, AVZO-021 demonstrated efficacy in in vivo xenograft models, both as a single agent and in combination with CDK4/6 inhibitors. Allorion disclosed select data in poster presentations at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in October 2023.

On January 4, 2024 OnCusp Therapeutics, Inc., a biopharmaceutical company dedicated to transforming cutting-edge preclinical innovation into clinically validated treatments for cancer patients worldwide, reported an oversubscribed $100 million Series A financing round (Press release, OnCusp Therapeutics, JAN 4, 2024, View Source [SID1234638990]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The round was co-led by Novo Holdings, OrbiMed, and F-Prime Capital, alongside Sofinnova Investments, Catalio Capital Management, Marshall Wace, Forge Life Science Partners, Blackbird BioVentures, CJNV BioVenture and others, as well as BioTrack Capital, a co-lead for the Seed Round. OnCusp Therapeutics has raised $139 million since its establishment in April 2021. The proceeds from this financing will be used to advance CUSP06, an ADC targeting CDH6, toward clinical proof-of-concept. Additionally, the capital will aid in expanding the OnCusp portfolio and team.

CUSP06 has strong preclinical data demonstrating the potential for best-in-class activity. Engineered to increase potency, heighten "bystander effect," elevate linker stability, and overcome drug resistance, CUSP06’s differentiating attributes could translate into higher clinical response rates and durability, with an improved safety profile. Having obtained FDA IND clearance in 3Q 2023, CUSP06 will be in a first-in-human Phase I study in the US.

"We are grateful to have the trust and support from some of the most prominent global biotech investors," said Dr. Bing Yuan, Co-Founder and CEO of OnCusp Therapeutics. "I am also thankful to the OnCusp team for their commitment and excellent work. We hold a strong conviction to develop innovative oncology therapies for patients. This significant Series A financing enables OnCusp to accelerate the development of CUSP06 and other game-changing therapeutics in our fight against cancer."

As part of the financing, OnCusp Therapeutics will appoint Dr. Karen Hong, Partner in the Venture Investments team at Novo Holdings US, Inc., a wholly owned subsidiary of Novo Holdings; Diyong Xu, Principal at OrbiMed; and Dr. Chong Xu, Partner at F-Prime Capital, to the company’s Board of Directors.

"We are thrilled to have co-led this round. The remarkable progress that the company has made in such a short time is a testament to its highly efficient business model and the team’s exceptional execution capabilities," said Dr. Karen Hong. "We share OnCusp’s mission in bringing oncology innovations to life and are committed to supporting the company’s continued growth and success."

"ADCs have become one of the most promising modalities for treating cancer, and CDH6 is emerging as a winning ADC target. We believe CUSP06 is well positioned to unlock the full potential of this target, both in high and low CDH6 expressing tumors," said Diyong Xu. "We also look forward to OnCusp expanding its portfolio to fully leverage its translational and clinical development expertise."

"I am excited to join the OnCusp Board at this transformative moment for the company," stated Dr. Chong Xu. "F-Prime is committed to proactively champion breakthrough approaches like CUSP06, which holds immense potential to help patients with ovarian cancer and other advanced solid tumors. I look forward to working with other board members and the executive team to propel OnCusp to its next phase of growth."

"As a major investor since the company’s inception, I am impressed by the entrepreneurship, commitment, and perseverance exemplified by the OnCusp team in the current challenging biotech market." added Dr. Jiacong Guo, one of OnCusp’s current Board Directors and a Principal at BioTrack Capital. "I believe companies who are leading their field will emerge triumphant in their mission. I am confident that OnCusp is one of those companies."